Psychopharmacology

, Volume 235, Issue 1, pp 121–134 | Cite as

Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats

  • H. Schoch
  • M. Y. Huerta
  • C. M. Ruiz
  • M. R. Farrell
  • K. M. Jung
  • J. J. Huang
  • R. R. Campbell
  • D. Piomelli
  • S. V. Mahler
Original Investigation

Abstract

Rationale

Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like “Spice” cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc).

Objectives and methods

Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30–43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+).

Results

WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment.

Conclusions

These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

Keywords

Autoshaping Palatable food Novelty Endocannabinoid Nucleus accumbens Reward 

Notes

Acknowledgements

We thank Erik Castillo, Jenny Cevallos, Stephanie Lenogue, Iohana Pagnoncelli, Gagandeep Lal, Christopher Cross, and Richard Dang for the assistance in treating adolescent rats, behavioral testing, behavioral scoring, and sample preparation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. Abboussi O, Tazi A, Paizanis E, El Ganouni S (2014) Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis. Pharmacol Biochem Behav 120:95–102CrossRefPubMedGoogle Scholar
  2. Achterberg EJM, van Swieten MMH, Driel NV, Trezza V, Vanderschuren L (2016) Dissociating the role of endocannabinoids in the pleasurable and motivational properties of social play behaviour in rats. Pharmacol Res 110:151–158CrossRefPubMedPubMedCentralGoogle Scholar
  3. Astarita G, Ahmed F, Piomelli D (2009) Lipidomic analysis of biological samples by liquid chromatography coupled to mass spectrometry. Methods Mol Biol 579:201–219CrossRefPubMedGoogle Scholar
  4. Baldo BA, Pratt WE, Will MJ, Hanlon EC, Bakshi VP, Cador M (2013) Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior. Neurosci Biobehav Rev 37:1985–1998CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bambico FR, Nguyen NT, Katz N, Gobbi G (2010) Chronic exposure to cannabinoids during adolescence but not during adulthood impairs emotional behaviour and monoaminergic neurotransmission. Neurobiol Dis 37:641–655CrossRefPubMedGoogle Scholar
  6. Bardo MT, Neisewander JL, Kelly TH (2013) Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharmacol Rev 65:255–290CrossRefPubMedPubMedCentralGoogle Scholar
  7. Becker JB (2009) Sexual differentiation of motivation: a novel mechanism? Horm Behav 55:646–654CrossRefPubMedPubMedCentralGoogle Scholar
  8. Behan AT, Hryniewiecka M, O'Tuathaigh CM, Kinsella A, Cannon M, Karayiorgou M, Gogos JA, Waddington JL, Cotter DR (2012) Chronic adolescent exposure to delta-9-tetrahydrocannabinol in COMT mutant mice: impact on indices of dopaminergic, endocannabinoid and GABAergic pathways. Neuropsychopharmacology 37:1773–1783CrossRefPubMedPubMedCentralGoogle Scholar
  9. Belin D, Berson N, Balado E, Piazza PV, Deroche-Gamonet V (2011) High-novelty-preference rats are predisposed to compulsive cocaine self-administration. Neuropsychopharmacology 36:569–579CrossRefPubMedGoogle Scholar
  10. Belin D, Deroche-Gamonet V (2012) Responses to novelty and vulnerability to cocaine addiction: contribution of a multi-symptomatic animal model. Cold Spring Harb Perspect Med.  https://doi.org/10.1101/cshperspect.a011940
  11. Biscaia M, Marin S, Fernandez B, Marco EM, Rubio M, Guaza C, Ambrosio E, Viveros MP (2003) Chronic treatment with CP 55,940 during the peri-adolescent period differentially affects the behavioural responses of male and female rats in adulthood. Psychopharmacology 170:301–308CrossRefPubMedGoogle Scholar
  12. Blanco-Gandia MC, Mateos-Garcia A, Garcia-Pardo MP, Montagud-Romero S, Rodriguez-Arias M, Minarro J, Aguilar MA (2015) Effect of drugs of abuse on social behaviour: a review of animal models. Behav Pharmacol 26:541–570CrossRefPubMedGoogle Scholar
  13. Bossong MG, Niesink RJ (2010) Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol 92:370–385CrossRefPubMedGoogle Scholar
  14. Brenhouse HC, Andersen SL (2011) Developmental trajectories during adolescence in males and females: a cross-species understanding of underlying brain changes. Neurosci Biobehav Rev 35:1687–1703CrossRefPubMedPubMedCentralGoogle Scholar
  15. Caballero A, Tseng KY (2012) Association of cannabis use during adolescence, prefrontal cb1 receptor signaling, and schizophrenia. Front Pharmacol 3:101CrossRefPubMedPubMedCentralGoogle Scholar
  16. Caballero A, Tseng KY (2016) GABAergic function as a limiting factor for prefrontal maturation during adolescence. Trends Neurosci 39:441–448CrossRefPubMedPubMedCentralGoogle Scholar
  17. Cain ME, Saucier DA, Bardo MT (2005) Novelty seeking and drug use: contribution of an animal model. Exp Clin Psychopharmacol 13:367–375CrossRefPubMedGoogle Scholar
  18. Chen K, Kandel DB (1995) The natural history of drug use from adolescence to the mid-thirties in a general population sample. Am J Public Health 85:41–47CrossRefPubMedPubMedCentralGoogle Scholar
  19. Cuttler C, Spradlin A (2017) Measuring cannabis consumption: Psychometric properties of the Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQ-CU). PLoS One 12:e0178194CrossRefPubMedPubMedCentralGoogle Scholar
  20. De Petrocellis L, Orlando P, Moriello AS, Aviello G, Stott C, Izzo AA, Di Marzo V (2012) Cannabinoid actions at TRPV channels: effects on TRPV3 and TRPV4 and their potential relevance to gastrointestinal inflammation. Acta Physiol 204:255–266CrossRefGoogle Scholar
  21. Deminiere JM, Piazza PV, Le Moal M, Simon H (1989) Experimental approach to individual vulnerability to psychostimulant addiction. Neurosci Biobehav Rev 13:141–147CrossRefPubMedGoogle Scholar
  22. Di Marzo V, Ligresti A, Cristino L (2009) The endocannabinoid system as a link between homoeostatic and hedonic pathways involved in energy balance regulation. Int J Obes (Lond) 33(Suppl 2):S18–S24CrossRefGoogle Scholar
  23. Doremus-Fitzwater TL, Spear LP (2016) Reward-centricity and attenuated aversions: an adolescent phenotype emerging from studies in laboratory animals. Neurosci Biobehav Rev 70:121–134CrossRefPubMedPubMedCentralGoogle Scholar
  24. Dow-Edwards D, Silva L (2017) Endocannabinoids in brain plasticity: cortical maturation, HPA axis function and behavior. Brain Res 1654:157–164CrossRefPubMedGoogle Scholar
  25. Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, Devi LA, Hurd YL (2008) Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol 18:826–834CrossRefPubMedPubMedCentralGoogle Scholar
  26. Ellgren M, Spano SM, Hurd YL (2007) Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology 32:607–615CrossRefPubMedGoogle Scholar
  27. Flagel SB, Clark JJ, Robinson TE, Mayo L, Czuj A, Willuhn I, Akers CA, Clinton SM, Phillips PE, Akil H (2011) A selective role for dopamine in stimulus-reward learning. Nature 469:53–57CrossRefPubMedGoogle Scholar
  28. Gomes FV, Guimaraes FS, Grace AA (2015) Effects of pubertal cannabinoid administration on attentional set-shifting and dopaminergic hyper-responsivity in a developmental disruption model of schizophrenia. Int J Neuropsychopharmacol.  https://doi.org/10.1093/ijnp/pyu018.
  29. Higuera-Matas A, Soto-Montenegro ML, del Olmo N, Miguens M, Torres I, Vaquero JJ, Sanchez J, Garcia-Lecumberri C, Desco M, Ambrosio E (2008) Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence. Neuropsychopharmacology 33:806–813CrossRefPubMedGoogle Scholar
  30. Hurd YL, Michaelides M, Miller ML, Jutras-Aswad D (2014) Trajectory of adolescent cannabis use on addiction vulnerability. Neuropharmacology 76(Pt B):416–424CrossRefPubMedGoogle Scholar
  31. Jager G, Ramsey NF (2008) Long-term consequences of adolescent cannabis exposure on the development of cognition, brain structure and function: an overview of animal and human research. Curr Drug Abuse Rev 1:114–123CrossRefPubMedGoogle Scholar
  32. Jenkins HM, Moore BR (1973) The form of the auto-shaped response with food or water reinforcers. J Exp Anal Behav 20:163–181CrossRefPubMedPubMedCentralGoogle Scholar
  33. King CP, Palmer AA, Woods LC, Hawk LW, Richards JB, Meyer PJ (2016) Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats. Psychopharmacology 233:2593–2605CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kirkham TC, Williams CM, Fezza F, Di Marzo V (2002) Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 136:550–557CrossRefPubMedPubMedCentralGoogle Scholar
  35. Lau BK, Cota D, Cristino L, Borgland SL (2017) Endocannabinoid modulation of homeostatic and non-homeostatic feeding circuits. Neuropharmacology 124:38-51.  https://doi.org/10.1016/j.neuropharm.2017.05.033
  36. Laviolette SR, Grace AA (2006) The roles of cannabinoid and dopamine receptor systems in neural emotional learning circuits: implications for schizophrenia and addiction. Cell Mol Life Sci 63:1597–1613CrossRefPubMedGoogle Scholar
  37. Lee TT, Gorzalka BB (2012) Timing is everything: evidence for a role of corticolimbic endocannabinoids in modulating hypothalamic-pituitary-adrenal axis activity across developmental periods. Neuroscience 204:17–30CrossRefPubMedGoogle Scholar
  38. Llorente-Berzal A, Fuentes S, Gagliano H, Lopez-Gallardo M, Armario A, Viveros MP, Nadal R (2011) Sex-dependent effects of maternal deprivation and adolescent cannabinoid treatment on adult rat behaviour. Addict Biol 16:624–637CrossRefPubMedGoogle Scholar
  39. Lovic V, Saunders BT, Yager LM, Robinson TE (2011) Rats prone to attribute incentive salience to reward cues are also prone to impulsive action. Behav Brain Res 223:255–261CrossRefPubMedPubMedCentralGoogle Scholar
  40. Lowin T, Pongratz G, Straub RH (2016) The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts by activating CB2, TRPV1, TRPA1 and yet unidentified receptor targets. J Inflamm (Lond) 13:15CrossRefGoogle Scholar
  41. Lubman DI, Cheetham A, Yucel M (2015) Cannabis and adolescent brain development. Pharmacol Ther 148:1–16CrossRefPubMedGoogle Scholar
  42. Mahler SV, Berridge KC (2009) Which cue to “want?” Central amygdala opioid activation enhances and focuses incentive salience on a prepotent reward cue. J Neurosci 29:6500–6513CrossRefPubMedPubMedCentralGoogle Scholar
  43. Mahler SV, Smith KS, Berridge KC (2007) Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology 32:2267–2278CrossRefPubMedGoogle Scholar
  44. Maldonado R, Valverde O, Berrendero F (2006) Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 29:225–232CrossRefPubMedGoogle Scholar
  45. Meier MH, Caspi A, Ambler A, Harrington H, Houts R, Keefe RS, McDonald K, Ward A, Poulton R, Moffitt TE (2012) Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A 109:E2657–E2664CrossRefPubMedPubMedCentralGoogle Scholar
  46. Meyer PJ, Lovic V, Saunders BT, Yager LM, Flagel SB, Morrow JD, Robinson TE (2012) Quantifying individual variation in the propensity to attribute incentive salience to reward cues. PLoS One 7:e38987CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mokrysz C, Landy R, Gage SH, Munafo MR, Roiser JP, Curran HV (2016) Are IQ and educational outcomes in teenagers related to their cannabis use? A prospective cohort study. J Psychopharmacol 30:159–168CrossRefPubMedPubMedCentralGoogle Scholar
  48. Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W (2002) Cannabis use and mental health in young people: cohort study. BMJ 325:1195–1198CrossRefPubMedPubMedCentralGoogle Scholar
  49. Peterson GB, Ackilt JE, Frommer GP, Hearst ES (1972) Conditioned approach and contact behavior toward signals for food or brain-stimulation reinforcement. Science 177:1009–1011CrossRefPubMedGoogle Scholar
  50. Pistis M, Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL (2004) Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry 56:86–94CrossRefPubMedGoogle Scholar
  51. Pitchers KK, Phillips KB, Jones JL, Robinson TE, Sarter M (2017) Diverse roads to relapse: a discriminative cue signaling cocaine availability is more effective in renewing cocaine-seeking in goal-trackers than sign-trackers, and depends on basal forebrain cholinergic activity. J Neurosci. 37(30):7198–7208.  https://doi.org/10.1523/JNEUROSCI.0990-17.2017.
  52. Realini N, Vigano D, Guidali C, Zamberletti E, Rubino T, Parolaro D (2011) Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology 60:235–243CrossRefPubMedGoogle Scholar
  53. Renard J, Krebs MO, Le Pen G, Jay TM (2014) Long-term consequences of adolescent cannabinoid exposure in adult psychopathology. Front Neurosci 8:361CrossRefPubMedPubMedCentralGoogle Scholar
  54. Renard J, Rushlow WJ, Laviolette SR (2016a) What can rats tell us about adolescent cannabis exposure? Insights from preclinical research. Can J Psychiatry 61:328–334CrossRefPubMedPubMedCentralGoogle Scholar
  55. Renard J, Vitalis T, Rame M, Krebs MO, Lenkei Z, Le Pen G, Jay TM (2016b) Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol 26:55–64CrossRefPubMedGoogle Scholar
  56. Renard J, Rosen LG, Loureiro M, De Oliveira C, Schmid S, Rushlow WJ, Laviolette SR (2017) Adolescent cannabinoid exposure induces a persistent sub-cortical hyper-dopaminergic state and associated molecular adaptations in the prefrontal cortex. Cereb Cortex 27(2):1297–1310.  https://doi.org/10.1093/cercor/bhv335
  57. Robinson TE, Yager LM, Cogan ES, Saunders BT (2014) On the motivational properties of reward cues: individual differences. Neuropharmacology 76(Pt B):450–459CrossRefPubMedGoogle Scholar
  58. Rubino T, Parolaro D (2008) Long lasting consequences of cannabis exposure in adolescence. Mol Cell Endocrinol 286:S108–S113CrossRefPubMedGoogle Scholar
  59. Rubino T, Parolaro D (2015) Sex-dependent vulnerability to cannabis abuse in adolescence. Front Psychiatry 6:56CrossRefPubMedPubMedCentralGoogle Scholar
  60. Rubino T, Parolaro D (2016) The impact of exposure to cannabinoids in adolescence: insights from animal models. Biol Psychiatry 79(7):578–85.  https://doi.org/10.1016/j.biopsych.2015.07.024
  61. Rubino T, Vigano D, Realini N, Guidali C, Braida D, Capurro V, Castiglioni C, Cherubino F, Romualdi P, Candeletti S, Sala M, Parolaro D (2008) Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology 33:2760–2771CrossRefPubMedGoogle Scholar
  62. Rubino T, Zamberletti E, Parolaro D (2012) Adolescent exposure to cannabis as a risk factor for psychiatric disorders. J Psychopharmacol 26:177–188CrossRefPubMedGoogle Scholar
  63. Saunders BT, Robinson TE (2011) Individual variation in the motivational properties of cocaine. Neuropsychopharmacology 36:1668–1676CrossRefPubMedPubMedCentralGoogle Scholar
  64. Saunders BT, Robinson TE (2013) Individual variation in resisting temptation: implications for addiction. Neurosci Biobehav Rev 37:1955–1975CrossRefPubMedGoogle Scholar
  65. Saunders BT, Yager LM, Robinson TE (2013) Cue-evoked cocaine “craving”: role of dopamine in the accumbens core. J Neurosci 33:13989–14000CrossRefPubMedPubMedCentralGoogle Scholar
  66. Schneider M (2008) Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure. Addict Biol 13:253–263CrossRefPubMedGoogle Scholar
  67. Schneider M, Koch M (2003) Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28(10):1760–9Google Scholar
  68. Schneider M, Schomig E, Leweke FM (2008) Acute and chronic cannabinoid treatment differentially affects recognition memory and social behavior in pubertal and adult rats. Addict Biol 13:345–357CrossRefPubMedGoogle Scholar
  69. Scott JC, Wolf DH, Calkins ME, Bach EC, Weidner J, Ruparel K, Moore TM, Jones JD, Jackson CT, Gur RE, Gur RC (2017) Cognitive functioning of adolescent and young adult cannabis users in the Philadelphia Neurodevelopmental Cohort. Psychol Addict Behav 31:423–434CrossRefPubMedGoogle Scholar
  70. Shinohara Y, Inui T, Yamamoto T, Shimura T (2009) Cannabinoid in the nucleus accumbens enhances the intake of palatable solution. Neuroreport 20:1382–1385CrossRefPubMedGoogle Scholar
  71. Silva L, Black R, Michaelides M, Hurd YL, Dow-Edwards D (2016) Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: the unique susceptibility of the prepubescent animal. Neurotoxicol Teratol 58:88–100CrossRefPubMedGoogle Scholar
  72. Smith KS, Mahler SV, Pecina S, Berridge KC (2010) Hedonic hotspots: generating sensory pleasure in the brain. In: Berridge KC, Kringelbach ML (eds) Pleasures of the Brain. Oxford University Press, Oxford,UK pp 27–49Google Scholar
  73. Solinas M, Goldberg SR, Piomelli D (2008) The endocannabinoid system in brain reward processes. Br J Pharmacol 154:369–383CrossRefPubMedPubMedCentralGoogle Scholar
  74. Spear LP (2016) Consequences of adolescent use of alcohol and other drugs: studies using rodent models. Neurosci Biobehav Rev 70:228–243CrossRefPubMedPubMedCentralGoogle Scholar
  75. Stopponi S, Soverchia L, Ubaldi M, Cippitelli A, Serpelloni G, Ciccocioppo R (2014) Chronic THC during adolescence increases the vulnerability to stress-induced relapse to heroin seeking in adult rats. Eur Neuropsychopharmacol 24:1037–1045CrossRefPubMedGoogle Scholar
  76. Taylor M, Collin SM, Munafo MR, MacLeod J, Hickman M, Heron J (2017) Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: findings from a UK birth cohort. J Epidemiol Community Health. 71(8):764–770.  https://doi.org/10.1136/jech-2016-208503
  77. Tomasiewicz HC, Jacobs MM, Wilkinson MB, Wilson SP, Nestler EJ, Hurd YL (2012) Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability. Biol Psychiatry 72:803–810CrossRefPubMedPubMedCentralGoogle Scholar
  78. Trezza V, Baarendse PJ, Vanderschuren LJ (2014) On the interaction between drugs of abuse and adolescent social behavior. Psychopharmacology 231:1715–1729CrossRefPubMedGoogle Scholar
  79. Vlachou S, Panagis G (2014) Regulation of brain reward by the endocannabinoid system: a critical review of behavioral studies in animals. Curr Pharm Des 20:2072–2088CrossRefPubMedGoogle Scholar
  80. Wegener N, Koch M (2009) Behavioural disturbances and altered Fos protein expression in adult rats after chronic pubertal cannabinoid treatment. Brain Res 1253:81–91CrossRefPubMedGoogle Scholar
  81. Wei D, Lee D, Cox CD, Karsten CA, Penagarikano O, Geschwind DH, Gall CM, Piomelli D (2015) Endocannabinoid signaling mediates oxytocin-driven social reward. Proc Natl Acad Sci U S A 112:14084–14089CrossRefPubMedPubMedCentralGoogle Scholar
  82. Wiley JL, Burston JJ (2014) Sex differences in Delta(9)-tetrahydrocannabinol metabolism and in vivo pharmacology following acute and repeated dosing in adolescent rats. Neurosci Lett 576:51–55CrossRefPubMedPubMedCentralGoogle Scholar
  83. Wingo T, Nesil T, Choi JS, Li MD (2016) Novelty seeking and drug addiction in humans and animals: from behavior to molecules. J Neuroimmune Pharmacol 11:456–470CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • H. Schoch
    • 1
  • M. Y. Huerta
    • 1
  • C. M. Ruiz
    • 1
  • M. R. Farrell
    • 1
  • K. M. Jung
    • 2
  • J. J. Huang
    • 1
  • R. R. Campbell
    • 1
  • D. Piomelli
    • 2
  • S. V. Mahler
    • 1
  1. 1.Department of Neurobiology & BehaviorUniversity of CaliforniaIrvineUSA
  2. 2.Department of Anatomy & NeurobiologyUniversity of CaliforniaIrvineUSA

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