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Animal Models of Cannabis Use Disorder

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Cannabis Use Disorders

Abstract

Cannabis use has the potential to produce adverse physical and mental health effects and can result in cannabis use disorder (CUD). People affected by CUD have difficulty discontinuing cannabis use, and there are currently no approved medications for the treatment of CUD. Preclinical research in animals has been invaluable in uncovering neurobiological underpinnings of many neuropsychiatric disorders, as well as for the development of safe and effective medications. There are animal models available that can capture various aspects of cannabis abuse and detect signals that inform further development of CUD treatments. This chapter describes animal models available for the assessment of rewarding, relapse-inducing, subjective, and other abuse-related effects of cannabinoids and some of the findings obtained with these models.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

α7nACh:

Nicotinic acetylcholine receptor type alpha-7

A2A :

Adenosine receptor type A2A

AM4040:

Anandamide transport inhibitor

VDM11:

Anandamide transport inhibitor

CUD:

Cannabis use disorder

CB1 :

Cannabinoid receptor type 1

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (2013)

FAAH:

Fatty acid amide hydrolase

GABA:

Gamma-aminobutyric acid

THC:

Δ9-Tetrahydrocannabinol

CP 55,940:

A synthetic CB1 agonist

WIN 55,212:

A synthetic CB1 agonist

References

  1. Substance Abuse and Mental Health Services Administration. Results from the 2013 national survey on drug use and health: summary of national findings, NSDUH Series H-48. HHS Publication No (SMA) 14-4863. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.

    Google Scholar 

  2. Vandrey R, Dunn KE, Fry JA, Girling ER. A survey study to characterize use of spice products (synthetic cannabinoids). Drug Alcohol Depend. 2012;120(1–3):238–41.

    Article  CAS  PubMed  Google Scholar 

  3. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014;144:12–41.

    Article  CAS  PubMed  Google Scholar 

  4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

    Google Scholar 

  5. Brezing CA, Levin FR. The current state of pharmacological treatments for cannabis use disorder and withdrawal. Neuropsychopharmacology. 2018;43(1):173–94.

    Article  CAS  PubMed  Google Scholar 

  6. Hall W. What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? Addiction. 2015;110(1):19–35.

    Article  PubMed  Google Scholar 

  7. Karila L, Roux P, Rolland B, Benyamina A, Reynaud M, Aubin HJ, et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20(25):4112–8.

    Article  CAS  PubMed  Google Scholar 

  8. Heyman GM. Addiction: a disorder of choice. Cambridge, MA: Harvard University Press; 2009.

    Google Scholar 

  9. Park-Lee E, Lipari RN, Hedden SL, Kroutil LA, Porter JD. Receipt of services for substance use and mental health issues among adults: Results from the 2016 National Survey on Drug Use and Health. NSDUH Data Review. 2017. Retrieved from https://www.samhsa.gov/data/.

  10. Balter RE, Cooper ZD, Haney M. Novel pharmacologic approaches to treating cannabis use disorder. Curr Addict Rep. 2014;1(2):137–43.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Copeland J, Gates P, Pokorski I. A narrative review of psychological cannabis use treatments with and without pharmaceutical adjunct. Curr Pharm Des. 2016;22(42):6397–408.

    Article  CAS  PubMed  Google Scholar 

  12. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, et al. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001;58(4):322–8.

    Article  CAS  PubMed  Google Scholar 

  13. Metna-Laurent M, Mondesir M, Grel A, Vallee M, Piazza PV. Cannabinoid-induced tetrad in mice. Curr Protoc Neurosci. 2017;80:9.59.1–9.59.10.

    Article  Google Scholar 

  14. Branch MN, Dearing ME, Lee DM. Acute and chronic effects of delta 9-tetrahydrocannabinol on complex behavior of squirrel monkeys. Psychopharmacology. 1980;71(3):247–56.

    Article  CAS  PubMed  Google Scholar 

  15. Chaperon F, Thiebot MH. Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol. 1999;13(3):243–81.

    Article  CAS  PubMed  Google Scholar 

  16. Maldonado R. Study of cannabinoid dependence in animals. Pharmacol Ther. 2002;95(2):153–64.

    Article  CAS  PubMed  Google Scholar 

  17. Acri JB, Skolnick P. Pharmacotherapy of substance use disorders. In: Charney DS, Buxbaum JD, Sklar P, Nestler EJ, editors. Neurobiology of mental illness. 4th ed: Oxford University Press; 2013. p. 761–71.

    Google Scholar 

  18. Breiter HC, Rosen BR. Functional magnetic resonance imaging of brain reward circuitry in the human. Ann N Y Acad Sci. 1999;877:523–47.

    Article  CAS  PubMed  Google Scholar 

  19. Panlilio LV, Goldberg SR. Self-administration of drugs in animals and humans as a model and an investigative tool. Addiction. 2007;102(12):1863–70.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Griffiths RR. Common factors in human and infrahuman drug self-administration. Psychopharmacol Bull. 1980;16(1):45–7.

    CAS  PubMed  Google Scholar 

  21. Johanson CE, Balster RL. A summary of the results of a drug self-administration study using substitution procedures in rhesus monkeys. Bull Narc. 1978;30(3):43–54.

    CAS  PubMed  Google Scholar 

  22. Katz JL, Goldberg SR. Preclinical assessment of abuse liability of drugs. Agents Actions. 1988;23(1–2):18–26.

    Article  CAS  PubMed  Google Scholar 

  23. Takahashi RN, Singer G. Self-administration of delta 9-tetrahydrocannabinol by rats. Pharmacol Biochem Behav. 1979;11(6):737–40.

    Article  CAS  PubMed  Google Scholar 

  24. Takahashi RN, Singer G. Effects of body weight levels on cannabis self-injection. Pharmacol Biochem Behav. 1980;13(6):877–81.

    Article  CAS  PubMed  Google Scholar 

  25. van Ree JM, Slangen JL, de Wied D. Intravenous self-administration of drugs in rats. J Pharmacol Exp Ther. 1978;204(3):547–57.

    PubMed  Google Scholar 

  26. Murray JE, Bevins RA. Cannabinoid conditioned reward and aversion: behavioral and neural processes. ACS Chem Neurosci. 2010;1(4):265–78.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Fattore L, Cossu G, Martellotta CM, Fratta W. Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats. Psychopharmacology. 2001;156(4):410–6.

    Article  CAS  PubMed  Google Scholar 

  28. Lefever TW, Marusich JA, Antonazzo KR, Wiley JL. Evaluation of WIN 55,212-2 self-administration in rats as a potential cannabinoid abuse liability model. Pharmacol Biochem Behav. 2014;118:30–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W. Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice. Neuroscience. 1998;85(2):327–30.

    Article  CAS  PubMed  Google Scholar 

  30. Mendizabal V, Zimmer A, Maldonado R. Involvement of kappa/dynorphin system in WIN 55,212-2 self-administration in mice. Neuropsychopharmacology. 2006;31(9):1957–66.

    Article  CAS  PubMed  Google Scholar 

  31. Harris RT, Waters W, McLendon D. Evaluation of reinforcing capability of delta-9-tetrahydrocannabinol in rhesus monkeys. Psychopharmacologia. 1974;37(1):23–9.

    Article  CAS  PubMed  Google Scholar 

  32. Mansbach RS, Nicholson KL, Martin BR, Balster RL. Failure of Delta(9)-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys. Behav Pharmacol. 1994;5(2):219–25.

    Article  CAS  PubMed  Google Scholar 

  33. Pickens R, Thompson T, Muchow DC. Cannabis and phencyclidine self-administered by animals. In: Goldfarb L, Hoffmeister F, editors. Psychic dependence [Bayer-Symposium IV]. Berlin: Springer; 1973. p. 78–86.

    Chapter  Google Scholar 

  34. Justinova Z, Goldberg SR, Heishman SJ, Tanda G. Self-administration of cannabinoids by experimental animals and human marijuana smokers. Pharmacol Biochem Behav. 2005;81(2):285–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Panlilio LV, Justinova Z. Preclinical studies of cannabinoid reward, treatments for cannabis use disorder, and addiction-related effects of cannabinoid exposure. Neuropsychopharmacology. 2018;43(1):116–41.

    Article  CAS  PubMed  Google Scholar 

  36. Tanda G. Preclinical studies on the reinforcing effects of cannabinoids. A tribute to the scientific research of Dr. Steve Goldberg. Psychopharmacology. 2016;233(10):1845–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Justinova Z, Solinas M, Tanda G, Redhi GH, Goldberg SR. The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys. J Neurosci. 2005;25(23):5645–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Justinova Z, Tanda G, Redhi GH, Goldberg SR. Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology. 2003;169(2):135–40.

    Article  CAS  PubMed  Google Scholar 

  39. Justinova Z, Yasar S, Redhi GH, Goldberg SR. The endogenous cannabinoid 2-arachidonoylglycerol is intravenously self-administered by squirrel monkeys. J Neurosci. 2011;31(19):7043–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Tanda G, Munzar P, Goldberg SR. Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci. 2000;3(11):1073–4.

    Article  CAS  PubMed  Google Scholar 

  41. Panlilio LV, Justinova Z, Goldberg SR. Animal models of cannabinoid reward. Br J Pharmacol. 2010;160(3):499–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tanda G, Goldberg SR. Cannabinoids: reward, dependence, and underlying neurochemical mechanisms – a review of recent preclinical data. Psychopharmacology. 2003;169(2):115–34.

    Article  CAS  PubMed  Google Scholar 

  43. Deiana S, Fattore L, Spano MS, Cossu G, Porcu E, Fadda P, et al. Strain and schedule-dependent differences in the acquisition, maintenance and extinction of intravenous cannabinoid self-administration in rats. Neuropharmacology. 2007;52(2):646–54.

    Article  CAS  PubMed  Google Scholar 

  44. Fattore L, Spano MS, Altea S, Angius F, Fadda P, Fratta W. Cannabinoid self-administration in rats: sex differences and the influence of ovarian function. Br J Pharmacol. 2007;152(5):795–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fattore L, Spano MS, Altea S, Fadda P, Fratta W. Drug- and cue-induced reinstatement of cannabinoid-seeking behaviour in male and female rats: influence of ovarian hormones. Br J Pharmacol. 2010;160(3):724–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Justinova Z, Mangieri RA, Bortolato M, Chefer SI, Mukhin AG, Clapper JR, et al. Fatty acid amide hydrolase inhibition heightens anandamide signaling without producing reinforcing effects in primates. Biol Psychiatry. 2008;64(11):930–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Justinova Z, Panlilio LV, Moreno-Sanz G, Redhi GH, Auber A, Secci ME, et al. Effects of fatty acid amide hydrolase (FAAH) inhibitors in non-human primate models of nicotine reward and relapse. Neuropsychopharmacology. 2015;40(9):2185–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schindler CW, Scherma M, Redhi GH, Vadivel SK, Makriyannis A, Goldberg SR, et al. Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys. Psychopharmacology. 2016;233(10):1867–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Justinova Z, Mascia P, Wu HQ, Secci ME, Redhi GH, Panlilio LV, et al. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nat Neurosci. 2013;16(11):1652–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Justinova Z, Redhi GH, Goldberg SR, Ferre S. Differential effects of presynaptic versus postsynaptic adenosine A2A receptor blockade on Delta9-tetrahydrocannabinol (THC) self-administration in squirrel monkeys. J Neurosci. 2014;34(19):6480–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Justinova Z, Munzar P, Panlilio LV, Yasar S, Redhi GH, Tanda G, et al. Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB(1)-receptor antagonist rimonabant. Neuropsychopharmacology. 2008;33(12):2870–7.

    Article  CAS  PubMed  Google Scholar 

  52. Everitt BJ, Robbins TW. Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour. Psychopharmacology. 2000;153(1):17–30.

    Article  CAS  PubMed  Google Scholar 

  53. Schindler CW, Panlilio LV, Goldberg SR. Second-order schedules of drug self-administration in animals. Psychopharmacology. 2002;163(3–4):327–44.

    Article  CAS  PubMed  Google Scholar 

  54. Bossert JM, Marchant NJ, Calu DJ, Shaham Y. The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology. 2013;229(3):453–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD, et al. Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status. Biol Psychiatry. 2013;73(3):242–8.

    Article  PubMed  Google Scholar 

  56. Venniro M, Caprioli D, Shaham Y. Animal models of drug relapse and craving: From drug priming-induced reinstatement to incubation of craving after voluntary abstinence. Prog Brain Res. 2016;224:25–52.

    Article  PubMed  Google Scholar 

  57. Schindler CW, Redhi GH, Vemuri K, Makriyannis A, Le Foll B, Bergman J, et al. Blockade of nicotine and cannabinoid reinforcement and relapse by a cannabinoid CB1-receptor neutral antagonist AM4113 and inverse agonist rimonabant in squirrel monkeys. Neuropsychopharmacology. 2016;41(9):2283–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Justinova Z, Tanda G, Munzar P, Goldberg SR. The opioid antagonist naltrexone reduces the reinforcing effects of Delta 9 tetrahydrocannabinol (THC) in squirrel monkeys. Psychopharmacology. 2004;173(1–2):186–94.

    CAS  PubMed  Google Scholar 

  59. Justinova Z, Ferre S, Redhi GH, Mascia P, Stroik J, Quarta D, et al. Reinforcing and neurochemical effects of cannabinoid CB1 receptor agonists, but not cocaine, are altered by an adenosine A2A receptor antagonist. Addict Biol. 2011;16(3):405–15.

    Article  CAS  PubMed  Google Scholar 

  60. Solinas M, Scherma M, Fattore L, Stroik J, Wertheim C, Tanda G, et al. Nicotinic alpha 7 receptors as a new target for treatment of cannabis abuse. J Neurosci. 2007;27(21):5615–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Justinova Z, Mascia P, Secci ME, Redhi GH, Piomelli D, Goldberg SR. The FAAH inhibitor PF-04457845 has THC-like rewarding and reinstatement effects in squirrel monkeys and increases dopamine levels in the nucleus accumbens shell in rats. FASEB J. 2014;28:838.6.

    Google Scholar 

  62. Panlilio LV, Thorndike EB, Nikas SP, Alapafuja SO, Bandiera T, Cravatt BF, et al. Effects of fatty acid amide hydrolase (FAAH) inhibitors on working memory in rats. Psychopharmacology. 2016;233(10):1879–88.

    Article  CAS  PubMed  Google Scholar 

  63. Navarro M, Carrera MR, Fratta W, Valverde O, Cossu G, Fattore L, et al. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci. 2001;21(14):5344–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Fadda P, Scherma M, Spano MS, Salis P, Melis V, Fattore L, et al. Cannabinoid self-administration increases dopamine release in the nucleus accumbens. Neuroreport. 2006;17(15):1629–32.

    Article  CAS  PubMed  Google Scholar 

  65. Kirschmann EK, Pollock MW, Nagarajan V, Torregrossa MM. Effects of adolescent cannabinoid self-administration in rats on addiction-related behaviors and working memory. Neuropsychopharmacology. 2017;42(5):989–1000.

    Article  CAS  PubMed  Google Scholar 

  66. De Luca MA, Bimpisidis Z, Melis M, Marti M, Caboni P, Valentini V, et al. Stimulation of in vivo dopamine transmission and intravenous self-administration in rats and mice by JWH-018, a spice cannabinoid. Neuropharmacology. 2015;99:705–14.

    Article  PubMed  CAS  Google Scholar 

  67. De Luca MA, Valentini V, Bimpisidis Z, Cacciapaglia F, Caboni P, Di Chiara G. Endocannabinoid 2-Arachidonoylglycerol self-administration by Sprague-Dawley rats and stimulation of in vivo dopamine transmission in the nucleus Accumbens Shell. Front Psych. 2014;5:140.

    Google Scholar 

  68. Covey DP, Wenzel JM, Cheer JF. Cannabinoid modulation of drug reward and the implications of marijuana legalization. Brain Res. 2014;1628:233–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Spano MS, Fattore L, Cossu G, Deiana S, Fadda P, Fratta W. CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat. Br J Pharmacol. 2004;143(3):343–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Struik D, Fadda P, Zara T, Zamberletti E, Rubino T, Parolaro D, et al. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function. Pharmacol Res. 2017;115:209–17.

    Article  CAS  PubMed  Google Scholar 

  71. Pickens CL, Airavaara M, Theberge F, Fanous S, Hope BT, Shaham Y. Neurobiology of the incubation of drug craving. Trends Neurosci. 2011;34(8):411–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Grimm JW, Hope BT, Wise RA, Neuroadaptation SY. Incubation of cocaine craving after withdrawal. Nature. 2001;412(6843):141–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Caprioli D, Venniro M, Zeric T, Li X, Adhikary S, Madangopal R, et al. Effect of the novel positive allosteric modulator of metabotropic glutamate receptor 2 AZD8529 on incubation of methamphetamine craving after prolonged voluntary abstinence in a rat model. Biol Psychiatry. 2015;78(7):463–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cheer JF, Marsden CA, Kendall DA, Mason R. Lack of response suppression follows repeated ventral tegmental cannabinoid administration: an in vitro electrophysiological study. Neuroscience. 2000;99(4):661–7.

    Article  CAS  PubMed  Google Scholar 

  75. Klein C, Karanges E, Spiro A, Wong A, Spencer J, Huynh T, et al. Cannabidiol potentiates Delta(9)-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. Psychopharmacology. 2011;218(2):443–57.

    Article  CAS  PubMed  Google Scholar 

  76. Polissidis A, Chouliara O, Galanopoulos A, Marselos M, Papadopoulou-Daifoti Z, Antoniou K. Behavioural and dopaminergic alterations induced by a low dose of WIN 55,212-2 in a conditioned place preference procedure. Life Sci. 2009;85(5–6):248–54.

    Article  CAS  PubMed  Google Scholar 

  77. Robinson L, Hinder L, Pertwee RG, Riedel G. Effects of delta9-THC and WIN-55,212-2 on place preference in the water maze in rats. Psychopharmacology. 2003;166(1):40–50.

    Article  CAS  PubMed  Google Scholar 

  78. Vlachou S, Nomikos GG, Stephens DN, Panagis G. Lack of evidence for appetitive effects of Delta 9-tetrahydrocannabinol in the intracranial self-stimulation and conditioned place preference procedures in rodents. Behav Pharmacol. 2007;18(4):311–9.

    Article  CAS  PubMed  Google Scholar 

  79. Panagis G, Mackey B, Vlachou S. Cannabinoid regulation of brain reward processing with an emphasis on the role of CB1 receptors: a step back into the future. Front Psych. 2014;5:92.

    Google Scholar 

  80. Lepore M, Vorel SR, Lowinson J, Gardner EL. Conditioned place preference induced by delta 9-tetrahydrocannabinol: comparison with cocaine, morphine, and food reward. Life Sci. 1995;56(23–24):2073–80.

    Article  CAS  PubMed  Google Scholar 

  81. Hempel BJ, Wakeford AG, Clasen MM, Friar MA, Riley AL. Delta-9-tetrahydrocannabinol (THC) history fails to affect THC’s ability to induce place preferences in rats. Pharmacol Biochem Behav. 2016;144:1–6.

    Article  CAS  PubMed  Google Scholar 

  82. Hyatt WS, Fantegrossi WE. Delta9-THC exposure attenuates aversive effects and reveals appetitive effects of K2/'Spice' constituent JWH-018 in mice. Behav Pharmacol. 2014;25(3):253–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wakeford AG, Flax SM, Pomfrey RL, Riley AL. Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats. Pharmacol Biochem Behav. 2016;140:75–81.

    Article  CAS  PubMed  Google Scholar 

  84. Parker LA, McDonald RV. Reinstatement of both a conditioned place preference and a conditioned place aversion with drug primes. Pharmacol Biochem Behav. 2000;66(3):559–61.

    Article  CAS  PubMed  Google Scholar 

  85. Colpaert FC. Drug discrimination in neurobiology. Pharmacol Biochem Behav. 1999;64(2):337–45.

    Article  CAS  PubMed  Google Scholar 

  86. Solinas M, Panlilio LV, Justinova Z, Yasar S, Goldberg SR. Using drug-discrimination techniques to study the abuse-related effects of psychoactive drugs in rats. Nat Protoc. 2006;1(3):1194–206.

    Article  CAS  PubMed  Google Scholar 

  87. Wiley JL, Owens RA, Lichtman AH. Discriminative stimulus properties of phytocannabinoids, endocannabinoids, and synthetic cannabinoids. Curr Top Behav Neurosci. Springer, Cham. 2016.

    Chapter  Google Scholar 

  88. Balster RL, Prescott WR. Delta 9-tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication. Neurosci Biobehav Rev. 1992;16(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  89. Jarbe TU, Hiltunen AJ. Limited stimulus generalization between delta 9-THC and diazepam in pigeons and gerbils. Psychopharmacology. 1988;94(3):328–31.

    Article  CAS  PubMed  Google Scholar 

  90. Solinas M, Goldberg SR. Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology. 2005;179(4):804–12.

    Article  CAS  PubMed  Google Scholar 

  91. Solinas M, Tanda G, Wertheim CE, Goldberg SR. Dopaminergic augmentation of delta-9-tetrahydrocannabinol (THC) discrimination: possible involvement of D(2)-induced formation of anandamide. Psychopharmacology. 2010;209(2):191–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jarbe TU, Gifford RS. "herbal incense": designer drug blends as cannabimimetics and their assessment by drug discrimination and other in vivo bioassays. Life Sci. 2014;97(1):64–71.

    Article  CAS  PubMed  Google Scholar 

  93. Wiley JL, Lefever TW, Cortes RA, Marusich JA. Cross-substitution of Delta9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats. Pharmacol Biochem Behav. 2014;124:123–8.

    Article  CAS  PubMed  Google Scholar 

  94. Wiley JL, Lefever TW, Marusich JA, Craft RM. Comparison of the discriminative stimulus and response rate effects of (Delta9)-tetrahydrocannabinol and synthetic cannabinoids in female and male rats. Drug Alcohol Depend. 2017;172:51–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wiley JL, Matthew Walentiny D, Vann RE, Baskfield CY. Dissimilar cannabinoid substitution patterns in mice trained to discriminate Delta(9)-tetrahydrocannabinol or methanandamide from vehicle. Behav Pharmacol. 2011;22(5–6):480–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Solinas M, Tanda G, Justinova Z, Wertheim CE, Yasar S, Piomelli D, et al. The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase but not by inhibition of anandamide transport. J Pharmacol Exp Ther. 2007;321(1):370–80.

    Article  CAS  PubMed  Google Scholar 

  97. Wise RA, Hoffman DC. Localization of drug reward mechanisms by intracranial injections. Synapse. 1992;10(3):247–63.

    Article  CAS  PubMed  Google Scholar 

  98. Braida D, Iosue S, Pegorini S, Sala M. Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats. Eur J Pharmacol. 2004;506(1):63–9.

    Article  CAS  PubMed  Google Scholar 

  99. Braida D, Pozzi M, Cavallini R, Sala M. Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system. Neuroscience. 2001;104(4):923–6.

    Article  CAS  PubMed  Google Scholar 

  100. Zangen A, Solinas M, Ikemoto S, Goldberg SR, Wise RA. Two brain sites for cannabinoid reward. J Neurosci. 2006;26(18):4901–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Solinas M, Zangen A, Thiriet N, Goldberg SR. Beta-endorphin elevations in the ventral tegmental area regulate the discriminative effects of Delta-9-tetrahydrocannabinol. Eur J Neurosci. 2004;19(12):3183–92.

    Article  CAS  PubMed  Google Scholar 

  102. Westerink BH. Brain microdialysis and its application for the study of animal behaviour. Behav Brain Res. 1995;70(2):103–24.

    Article  CAS  PubMed  Google Scholar 

  103. Lecca D, Cacciapaglia F, Valentini V, Di Chiara G. Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration. Psychopharmacology. 2006;188(1):63–74.

    Article  CAS  PubMed  Google Scholar 

  104. Chen JP, Paredes W, Lowinson JH, Gardner EL. Strain-specific facilitation of dopamine efflux by delta 9-tetrahydrocannabinol in the nucleus accumbens of rat: an in vivo microdialysis study. Neurosci Lett. 1991;129(1):136–80.

    Article  CAS  PubMed  Google Scholar 

  105. Tanda G, Pontieri FE, Di Chiara G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science. 1997;276(5321):2048–50.

    Article  CAS  PubMed  Google Scholar 

  106. Chen J, Marmur R, Pulles A, Paredes W, Gardner EL. Ventral tegmental microinjection of delta 9-tetrahydrocannabinol enhances ventral tegmental somatodendritic dopamine levels but not forebrain dopamine levels: evidence for local neural action by marijuana’s psychoactive ingredient. Brain Res. 1993;621(1):65–70.

    Article  CAS  PubMed  Google Scholar 

  107. Pistis M, Ferraro L, Pira L, Flore G, Tanganelli S, Gessa GL, et al. Delta(9)-tetrahydrocannabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the rat prefrontal cortex: an in vivo microdialysis study. Brain Res. 2002;948(1–2):155–8.

    Article  CAS  PubMed  Google Scholar 

  108. Parsons LH, Hurd YL. Endocannabinoid signalling in reward and addiction. Nat Rev Neurosci. 2015;16(10):579–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Caille S, Alvarez-Jaimes L, Polis I, Stouffer DG, Parsons LH. Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration. J Neurosci. 2007;27(14):3695–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Buczynski MW, Polis IY, Parsons LH. The volitional nature of nicotine exposure alters anandamide and oleoylethanolamide levels in the ventral tegmental area. Neuropsychopharmacology. 2013;38(4):574–84.

    Article  CAS  PubMed  Google Scholar 

  111. Cheer JF, Wassum KM, Heien ML, Phillips PE, Wightman RM. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci. 2004;24(18):4393–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Jacques S. Brain stimulation and reward: “pleasure centers” after twenty-five years. Neurosurgery. 1979;5(2):277–83.

    Article  CAS  PubMed  Google Scholar 

  113. Kornetsky C, Esposito RU, McLean S, Jacobson JO. Intracranial self-stimulation thresholds: a model for the hedonic effects of drugs of abuse. Arch Gen Psychiatry. 1979;36(3):289–92.

    Article  CAS  PubMed  Google Scholar 

  114. Gardner EL, Paredes W, Smith D, Donner A, Milling C, Cohen D, et al. Facilitation of brain stimulation reward by delta 9-tetrahydrocannabinol. Psychopharmacology. 1988;96(1):142–4.

    Article  CAS  PubMed  Google Scholar 

  115. Lepore M, Liu X, Savage V, Matalon D, Gardner EL. Genetic differences in delta 9-tetrahydrocannabinol-induced facilitation of brain stimulation reward as measured by a rate-frequency curve-shift electrical brain stimulation paradigm in three different rat strains. Life Sci. 1996;58(25):PL365–72.

    Article  CAS  PubMed  Google Scholar 

  116. Vlachou S, Nomikos GG, Panagis G. CB1 cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat. Psychopharmacology. 2005;179(2):498–508.

    Article  CAS  PubMed  Google Scholar 

  117. Xi ZX, Spiller K, Pak AC, Gilbert J, Dillon C, Li X, et al. Cannabinoid CB1 receptor antagonists attenuate cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Neuropsychopharmacology. 2008;33(7):1735–45.

    Article  CAS  PubMed  Google Scholar 

  118. Harris AC, Muelken P, Smethells JR, Krueger M, LeSage MG. Similar precipitated withdrawal effects on intracranial self-stimulation during chronic infusion of an e-cigarette liquid or nicotine alone. Pharmacol Biochem Behav. 2017;161:1–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006;19(3):233–8.

    Article  PubMed  Google Scholar 

  120. Haney M. The marijuana withdrawal syndrome: diagnosis and treatment. Curr Psychiatry Rep. 2005;7(5):360–6.

    Article  PubMed  Google Scholar 

  121. Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction. 1999;94(9):1311–22.

    Article  CAS  PubMed  Google Scholar 

  122. Karschner EL, Schwilke EW, Lowe RH, Darwin WD, Herning RI, Cadet JL, et al. Implications of plasma Delta9-tetrahydrocannabinol, 11-hydroxy-THC, and 11-nor-9-carboxy-THC concentrations in chronic cannabis smokers. J Anal Toxicol. 2009;33(8):469–77.

    Article  CAS  PubMed  Google Scholar 

  123. Aceto MD, Scates SM, Martin BB. Spontaneous and precipitated withdrawal with a synthetic cannabinoid, WIN 55212-2. Eur J Pharmacol. 2001;416(1–2):75–81.

    Article  CAS  PubMed  Google Scholar 

  124. Aceto MD, Scates SM, Lowe JA, Martin BR. Dependence on delta 9-tetrahydrocannabinol: studies on precipitated and abrupt withdrawal. J Pharmacol Exp Ther. 1996;278(3):1290–5.

    CAS  PubMed  Google Scholar 

  125. Lichtman AH, Fisher J, Martin BR. Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. Pharmacol Biochem Behav. 2001;69(1–2):181–8.

    Article  CAS  PubMed  Google Scholar 

  126. Tai S, Nikas SP, Shukla VG, Vemuri K, Makriyannis A, Jarbe TU. Cannabinoid withdrawal in mice: inverse agonist vs neutral antagonist. Psychopharmacology. 2015;232(15):2751–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Fredericks AB, Benowitz NL. An abstinence syndrome following chronic administration of delta-9-terahydrocannabinol in rhesus monkeys. Psychopharmacology. 1980;71(2):201–2.

    Article  CAS  PubMed  Google Scholar 

  128. Stewart JL, McMahon LR. Rimonabant-induced Delta9-tetrahydrocannabinol withdrawal in rhesus monkeys: discriminative stimulus effects and other withdrawal signs. J Pharmacol Exp Ther. 2010;334(1):347–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Beardsley PM, Balster RL, Harris LS. Dependence on tetrahydrocannabinol in rhesus monkeys. J Pharmacol Exp Ther. 1986;239(2):311–9.

    CAS  PubMed  Google Scholar 

  130. Beardsley PM, Martin BR. Effects of the cannabinoid CB(1) receptor antagonist, SR141716A, after Delta(9)-tetrahydrocannabinol withdrawal. Eur J Pharmacol. 2000;387(1):47–53.

    Article  CAS  PubMed  Google Scholar 

  131. McMahon LR. Discriminative stimulus effects of the cannabinoid CB1 antagonist SR 141716A in rhesus monkeys pretreated with Delta9-tetrahydrocannabinol. Psychopharmacology. 2006;188(3):306–14.

    Article  CAS  PubMed  Google Scholar 

  132. Little PJ, Compton DR, Johnson MR, Melvin LS, Martin BR. Pharmacology and stereoselectivity of structurally novel cannabinoids in mice. J Pharmacol Exp Ther. 1988;247(3):1046–51.

    CAS  PubMed  Google Scholar 

  133. Wiley JL, Martin BR. Cannabinoid pharmacological properties common to other centrally acting drugs. Eur J Pharmacol. 2003;471(3):185–93.

    Article  CAS  PubMed  Google Scholar 

  134. Ibsen MS, Connor M, Glass M. Cannabinoid CB1 and CB2 receptor signaling and bias. Cannabis Cannabinoid Res. 2017;2(1):48–60.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Khurana L, Mackie K, Piomelli D, Kendall DA. Modulation of CB1 cannabinoid receptor by allosteric ligands: pharmacology and therapeutic opportunities. Neuropharmacology. 2017;124:3–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Crean RD, Crane NA, Mason BJ. An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med. 2011;5(1):1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Kangas BD, Bergman J. Touchscreen technology in the study of cognition-related behavior. Behav Pharmacol. 2017;28(8):623–9.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Kangas BD, Leonard MZ, Shukla VG, Alapafuja SO, Nikas SP, Makriyannis A, et al. Comparisons of Delta9-tetrahydrocannabinol and anandamide on a battery of cognition-related behavior in nonhuman primates. J Pharmacol Exp Ther. 2016;357(1):125–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The preparation of this manuscript was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health.

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  1. Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, NIDA, NIH, DHHS, Baltimore, MD, USA

    Zuzana Justinova

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  1. Zuzana Justinova
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  1. Division of Pharma & Med Cons Drug Abuse, NIDA, NIH, Department of Health & Human Services, Bethesda, MD, USA

    Ivan D. Montoya

  2. Division of Extramural Research, National Institute on Drug Abuse Division of Extramural Research, Bethesda, MD, USA

    Susan R. B. Weiss

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Justinova, Z. (2019). Animal Models of Cannabis Use Disorder. In: Montoya, I., Weiss, S. (eds) Cannabis Use Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-90365-1_8

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