Skip to main content
SpringerLink
Log in
Book cover

Addiction Mechanisms, Phenomenology and Treatment pp 1–14Cite as

The neurobiology of addiction

  • Conference paper

Summary

Drug addiction includes complex neurobiological and behavioural processes. Acute reinforcing effects of drugs of abuse are responsible for the initiation of drug addiction, whereas the negative consequences of drug abstinence have a crucial motivational significance for relapse and maintenance of the addictive process. The mesocorticolimbic system represents a common neuronal substrate for the reinforcing properties of drugs of abuse. Both dopamine and opioid transmission play a crucial role in this reward pathway. Common neuronal changes have also been reported during the abstinence to different drugs of abuse that could underlie the negative motivational effects of withdrawal. These changes include decreased dopaminergic activity in the mesolimbic system and a recruitment of the brain stress pathways. All drugs of abuse interact with these brain circuits by acting on different molecular and neurochemical mechanisms. The existence of bidirectional interactions between different drugs of abuse, such as opioids and cannabinoids, provides further findings to support this common neurobiological substrate for drug addictive processes.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Acquas E, Di Chiara G (1992) Depression of mesolimbic dopamine transmission and sensitization to morphine during opiate abstinence. J Neurochem 58: 1620–1625

    Article  PubMed  CAS  Google Scholar 

  • Acquas E, Carboni E, Di Chiara G (1991) Profound depression of mesolimbic dopamine release after morphine withdrawal in dependent rats. Eur J Pharmacol 193: 133–134

    Article  PubMed  CAS  Google Scholar 

  • Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27: 1–39

    Article  PubMed  CAS  Google Scholar 

  • Bourtchuladze R, Frenguelli B, Blendy J, Cioffi D, Schutz G, Silva AJ (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79: 59–68

    Article  PubMed  CAS  Google Scholar 

  • Braida D, Pozzi M, Parolaro D, Sala M (2001) Intracerebral self-administration of the cannabinoid receptor agonist CP 55:940 in the rat: interaction with the opioid system. Eur J Pharmacol 413: 227–234

    Article  PubMed  CAS  Google Scholar 

  • Castane A, Robledo P, Matifas A, Kieffer, Maldonado R (2003) Cannabinoid withdrawal syndrom is reduced in double mu and delta opioid receptor mice. Eur J Neurosci 17: 155–159

    Article  PubMed  Google Scholar 

  • Chen J, Nye HE, Kelz MB, Hiroi N, Nakabeppu Y, Hope BT, Nestler EJ (1995) Regulation of delta FosB and FosB-like proteins by electroconvulsive seizure and cocaine treatments. Mol Pharmacol 48: 880–889

    PubMed  CAS  Google Scholar 

  • Chen JP, Paredes W, Lowinson JH, Gardner EL (1991) Strain-specific facilitation of dopamine efflux by delta-tetrahydrocannabinol in the nucleus accumbens of rat: an in vivo microdialysis study. Neurosci Lett 129: 136–180

    Article  PubMed  CAS  Google Scholar 

  • Corrigall WA, Franklin KBJ, Coen KM, Clarke PBS (1992) The mesomlimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psycopharmacology 107: 285–289

    Article  CAS  Google Scholar 

  • Cummings S, Elde R, Ells J, Lindall A (1983) Corticotropin releasing factor immunore-activity is widely distributed within the central nervous system of the rat: an immuno-histochemical study. J Neurosci 3: 1355–1368

    PubMed  CAS  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drug abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 94: 5274–5278

    Google Scholar 

  • Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: electrophysiological and biochemical evidence. Proc Natl Acad Sci USA 90: 7966–7969

    Article  PubMed  CAS  Google Scholar 

  • Diana M, Pistis M, Muntoni A, Gessa G (1996) Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience 71: 411–415

    Article  PubMed  CAS  Google Scholar 

  • Eckardt MJ, File SE, Gessa GL, Grant KA, Guerri C, Hoffman PL, Kalant H, Koob GF, Li TK, Tabakoff B (1998) Effects of moderate alcohol consumption on the central nervous system. Alcohol Clin Exp Res 22: 998–1040

    Article  PubMed  CAS  Google Scholar 

  • Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward: the role of amygdala-ventral striatal subsystems. Ann NY Acad Sci 877: 412–438

    Article  PubMed  CAS  Google Scholar 

  • Gessa GL, Melis M, Muntoni AL, Diana M (1998) Cannabinoids activate mesolimbic dopamine neurons by an action on cannabinoid CB1 receptors. Eur J Pharmacol 341: 39–44

    Article  PubMed  CAS  Google Scholar 

  • Ghozland S, Matthes HW, Simonin F, Filliol D, Kieffer BL, Maldonado R (2002) Motivational effects of cannabinoids are mediated by mu-opioid and kappa-opioid receptors. J Neurosci 22: 1146–1154

    PubMed  CAS  Google Scholar 

  • Golberg SR, Munzar P, Justinova Z, Tanda G (2001) Effects of naltrexone on intravenous self-administration of delta-9-tetrahydrocannabinol (THC) by squirrel monkeys under fixed-ratio and second-order schedules. Int Cannab Res Soc Meeting, p l02

    Google Scholar 

  • Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci USA 93: 12040–12045

    Article  PubMed  CAS  Google Scholar 

  • Guitart X, Nestler EJ (1989) Identification of morphine-and cyclic AMP-regulated phosphoproteins (MARPPs) in the locus coeruleus and other regions of rat brain: regulation by acute and chronic morphine. J Neurosci 9: 4371–4387

    PubMed  CAS  Google Scholar 

  • Guitart X, Thompson MA, Mirante CK, Greenberg ME, Nestler EJ (1992) Regulation of cyclic AMP response element-binding protein (CREB) phosphorylation by acute and chronic morphine in the rat locus coeruleus. J Neurochem 58: 1168–1171

    Article  PubMed  CAS  Google Scholar 

  • Heyser CJ, Roberts AJ, Schulteis G, Koob GF (1999) Central administration of an opiate antagonist decreses oral ethanol self-administration in rats. Alcohol Clin Exp Res 23: 1468–1476

    Article  PubMed  CAS  Google Scholar 

  • Hilderbrand BE, Nomikos GG, Hertel P, Schilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not in the medial prefrontal cortex in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779: 214–225

    Article  Google Scholar 

  • Hine B, Friedman E, Torrelio M, Gershon S (1975a) Tetrahydrocanabinol-attenuated abstinence and induced rotation in morphine-dependent rats: possible involvement of dopamine. Neuropharmacology 14: 607–610

    Article  PubMed  CAS  Google Scholar 

  • Hine B, Friedman E, Torrelio M, Gershon S (1975b) Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol. Science 187: 443–445

    Article  PubMed  CAS  Google Scholar 

  • Hope BT, Nye HE, Kelz MB, Self DW, Iadarola MJ, Nakabeppu Y, Duman RS, Nestler EJ (1994) Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments. Neuron 13: 1235–1244

    Article  PubMed  CAS  Google Scholar 

  • Howlett AC, Fleming RM (1984) Cannabinoid inhibition of adenyly cyclase. Pharmacoloby of the response in neuroblastoma cel membranes. Mol Pharmacol 27: 429–439

    Google Scholar 

  • Hutcheson DM, Tzavara ET, Smadja C, Valjent E, Roques BP, Hanoune J, Maldonado R (1998) Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol. Br J Pharmacol 125: 1567–1577

    Article  PubMed  CAS  Google Scholar 

  • Hyman SE, Nestler EJ (1996) Initiation and adaptation: a paradigm for understanding psychotropic drug action. Am J Psychiatry 153: 151–162

    PubMed  CAS  Google Scholar 

  • Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2: 695–703

    Article  PubMed  CAS  Google Scholar 

  • Jaffe JH (1990) Trivializing dependence. Br J Addict 85: 1425–1427

    Article  PubMed  CAS  Google Scholar 

  • Karin M, Liu Z, Zandi E (1997) AP-1 function and regulation. Curr Opin Cell Biol 9:240–246

    Article  PubMed  CAS  Google Scholar 

  • Kaymakcalan S, Ayhan IH, Tulunay FC (1977) Naloxone-induced or postwithdrawal abstinence signs in delta9-tetrahydrocannabinol-tolerant rats. Psychopharmacology 55:243–249

    Article  PubMed  CAS  Google Scholar 

  • Kelz MB, Nestler EJ (2000) deltaFosB: a molecular switch underlying long-term neural plasticity. Curr Opin Neurol 13: 715–720

    Article  PubMed  CAS  Google Scholar 

  • Kelz MB, Chen J, Carlezon WA Jr, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ (1999) Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature 401: 272–276

    Article  PubMed  CAS  Google Scholar 

  • Koob G (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13: 170–177

    Article  Google Scholar 

  • Koob GF (1996) Drug addiction: the yin and yang of hedonic homeostasis. Neuron 16: 893–896

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (1999) Cocaine reward and dopamine receptors: love at first site. Arch Gen Psychiatry 56: 1107–1108

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242: 715–723

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278: 52–58

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, LeMoal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24: 97–129

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Stinus L, Le Moal M, Bloom FE (1989) Opponent process theory of motivation: neurobiological evidence from studies of opiate dependence. Neurosci Biobehav Rev 13: 135–140

    Article  PubMed  CAS  Google Scholar 

  • Kreek MJ, Ragunath J, Plevy S, Hamer D, Schneider B, Hartman N (1984) ACTH, Cortisol and beta-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans. Neuropeptides 5: 277–278

    Article  PubMed  CAS  Google Scholar 

  • Ledent C, Valverde O, Cossu G, Petitet F, Aubert JF, Beslot F, Bohme GA, Imperato A, Pedrazzini T, Roques BP, Vassart G, Fratta W, Parmetier M (1999) Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 283: 15–19

    Article  Google Scholar 

  • Lichtman AH, Sheikh SM, Loh HH, Martin BR (2001) Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)-tetrahydrocannabinol and morphine-dependent mice. J Pharmacol Exp Ther 298: 1007–1014

    PubMed  CAS  Google Scholar 

  • Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243: 1721–1724

    Article  PubMed  CAS  Google Scholar 

  • Maldonado R (2003) Opioid system involvement in cannabinoid tolerance and dependence. In: Maldonado R (ed) Molecular biology of drug addiction. Humana Press, Totowa, pp 221–245

    Google Scholar 

  • Maldonado R, Rodriguez de Fonseca F (2002) Cannabinoid addiction: behavioral models and neural correlates. J Neurosci 22: 3326–3331

    PubMed  CAS  Google Scholar 

  • Maldonado R, Stinus L, Gold LH, Koob GF (1992) Role of different brain structures in the expression of the physical morphine withdrawal syndrome. J Pharmacol Exp Ther 261: 669–677

    PubMed  CAS  Google Scholar 

  • Maldonado R, Blendy JA, Tzavara E, Gass P, Roques BP, Hanoune J, Schutz G (1996) Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB. Science 273: 657–659

    Article  PubMed  CAS  Google Scholar 

  • Martin M, Ledent C, Parmentier M, Maldonado R, Valverde O (2000) Cocaine but not morphine, induce conditioned place preference and sensitization to locomotor responses in CB-1 knockout mice. Eur J Neurosci 12: 4038–4046

    Article  PubMed  CAS  Google Scholar 

  • Matthews RT, German DC (1984) Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine. Neuroscience 11: 617–625

    Article  PubMed  CAS  Google Scholar 

  • Mereu G, Fadda F, Gessa GL (1984) Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats. Brain Res 292: 63–69

    Article  PubMed  CAS  Google Scholar 

  • Mereu G, Kong-Woo PY, Boi V, Gessa GL, Naes L, Westfall TC (1987) Preferential Stimulation of ventral tegmental dopaminergic neurons by nicotine. Eur J Pharmacol 141: 395–399

    Article  PubMed  CAS  Google Scholar 

  • Merlo-Pick E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F (1995) Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci 15: 5439–5447

    Google Scholar 

  • Moratalla R, Elibol B, Vallejo M, Graybiel AM (1996) Network-level changes in expression of inducible Fos-Jun proteins in the striatum during chronic cocaine treatment and withdrawal. Neuron 17: 147–156

    Article  PubMed  CAS  Google Scholar 

  • Navarro M, Chowen J, Rocio A, Carrera M, Del Arco I, Villanua MA, Martin Y, Roberts AJ, Koob GF, de Fonseca FR (1998) CBl cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats. Neuroreport 9: 3397–3402

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2: 119–128

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ, Tallman JF (1988) Chronic morphine treatment increases cyclic AMP-dependent protein kinase activity in the rat locus coeruleus. Mol Pharmacol 33:127–132

    Google Scholar 

  • Nestler EJ, Erdos JJ, Terwilliger R, Duman RS, Tallman JF (1989) Regulation of G proteins by chronic morphine in the rat locus coeruleus. Brain Res 476: 230–239

    Article  PubMed  CAS  Google Scholar 

  • Nye HE, Nestler EJ (1996) Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. Mol Pharmacol 49: 636–645

    PubMed  CAS  Google Scholar 

  • Nye HE, Hope BT, Kelz MB, Iadarola M, Nestler EJ (1995) Pharmacological studies of the regulation of chronic Fos-related antigen induction by cocaine in the striatum and nucleus accumbens. J Pharmacol Exp Ther 275: 1671–1680

    PubMed  CAS  Google Scholar 

  • Parsons LH, Smith AD, Justice JB Jr (1991) Basal extracellular dopamine is decreased in the rat nucleus accumbens during abstinence from chronic cocaine. Synapse 9: 60–65

    Article  PubMed  CAS  Google Scholar 

  • Petit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psycopharmacology 84: 167–173

    Article  Google Scholar 

  • Pfeffer AO, Samson HH (1988) Haloperidol and apomorphine effects on ethanol reinforcement in free-feeding rats. Pharmacol Biochem Behav 29: 343–350

    Article  PubMed  CAS  Google Scholar 

  • Picciotto M, Corrigal W (2002) Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics. J Neurosci 22: 3338–3341

    PubMed  CAS  Google Scholar 

  • Pich EM, Pagliusi SR, Tessari M, Talabot-Ayer D, Hooft HR, Chiamulera C (1997) Common neural substrates for the addictive properties of nicotine and cocaine. Science 275: 83–86

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Di Chiara G (1995) Intravenous cocaine, morphine, and amphetamine preferentially increase extra cellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc Natl Acad Sci USA 92: 12304–12308

    Article  PubMed  CAS  Google Scholar 

  • Pontieri FE, Tanda G, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382: 255–257

    Article  PubMed  CAS  Google Scholar 

  • Richards G, Schoch P, Haefely W (1991) Benzodiazepine receptors: new vistas. Semin Neurosci 3: 191–203

    Article  Google Scholar 

  • Robbe D, Alonso G, Duchamp F, Bockaert J, Manzoni OJ (2001) Localization and mechanisms of action of cannabinoid receptors at the glutamatergic synapses of the mouse nucleus accumbens. J Neurosci 21: 109–116

    PubMed  CAS  Google Scholar 

  • Roberts AJ, McArthur RA, Hull EE, Post C, Koob GF (1998) Effects of amperozoide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol. Psycopharmacology 137: 25–32

    Article  CAS  Google Scholar 

  • Roberts AJ, Heyser CJ, McDonald JS, Kieffer BL, Matthes HWD, Koob GF, Gold LH (2000) Mu opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther 293: 1002–1008

    PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18: 247–291

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez de Fonseca F, Carrera MRA, Navarro M, Koob GF, Weiss F (1997) Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 276: 2050–2054

    Article  Google Scholar 

  • Rossetti ZL, Hmaidan Y, Gessa GL (1992) Marked inhibition of mesolimbic dopamine release: a common feature of ethanol, morphine, cocaine and amphetamine abstinence in rats. Eur J Pharmacol 221: 227–234

    Article  PubMed  CAS  Google Scholar 

  • Rubino T, Vigano D, Massi P, Parolaro D (2000a) Changes in the cannabinoid receptor binding, G protein coupling, and cyclic AMP cascade in the CNS of rats tolerant to and dependent on the synthetic cannabinoid compound CP55,940. J Neurochem 75: 2080–2086

    Article  PubMed  CAS  Google Scholar 

  • Rubino T, Vigano’ D, Massi P, Spinello M, Zagato E, Giagnoni G, Parolaro D (2000b) Chronic delta-9-tetrahydrocannabinol treatment increases cAMP levels and cAMP-dependent protein kinase activity in some rat brain regions. Neuropharmacology 39:1331–1336

    Article  PubMed  CAS  Google Scholar 

  • Rudnick G, Clark J (1993) From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters. Biochim Biophys Acta 1144: 249–263

    Article  PubMed  CAS  Google Scholar 

  • Ryabinin AE, Wang YM (1998) Repeated alcohol administration differentially affects c-Fos and FosB protein immunoreactivity in DBA/2J mice. Alcohol Clin Exp Res 22: 1646–1654

    Article  PubMed  CAS  Google Scholar 

  • Schulteis G, Heyser CJ, Koob GF (1997) Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine treatment. Psychopharmacology 129: 56–65

    Article  PubMed  CAS  Google Scholar 

  • Sharma SK, Klee WA, Nirenberg M (1975) Dual regulation of adenylate cyclase accounts for narcotic tolerance and dependence. Proc Natl Acad Sci USA 75: 3092–3096

    Article  Google Scholar 

  • Shippenberg TS, Herz A, Spanagel R, Bals-Kubik R, Stein C (1992) Conditioning of opioid reinforcement: neuroanatomical and neurochemical susbstrates. Ann NY Acad Sci 654: 347–356

    Article  PubMed  CAS  Google Scholar 

  • Solomon RL, Corbit JD (1974) An apponent-process theory of motivation. I. Temporal dynamics of affect. Psychol Rev 81: 119–145

    Article  PubMed  CAS  Google Scholar 

  • Tanda G, Pontieri FE, Di Chiara (1997) Cannabinoid and heroin activation of mesolimbic dopamine transmisión by a common mu1 opioid receptor mechanism. Science 276: 2048–2050

    Article  PubMed  CAS  Google Scholar 

  • Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83: 393–411

    Article  PubMed  CAS  Google Scholar 

  • Tzavara ETH, Valjent E, Firmo C, Mas M, Beslot F, Defer N, Roques BP, Hanoune J, Maldonado R (2000) Cannabinoid withdrawal is dependent upon PKA activation in the cerebelum. Eur J Neurosci 12:1038–1046

    Article  PubMed  CAS  Google Scholar 

  • Ungless MA, Whistler JL, Malenka RC, Bonci A (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411: 583–587

    Article  PubMed  CAS  Google Scholar 

  • Valverde O, Maldonado R, Valjent E, Zimmer AM, Zimmer A (2000) Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice. J Neurosci 20: 9284–9289

    PubMed  CAS  Google Scholar 

  • Valverde O, Noble F, Beslot F, Daugé V, Fournié-Zaluski MC, Roques BP (2001) Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect. Eur J Neurosci 13: 1816–1824

    Article  PubMed  CAS  Google Scholar 

  • Van Ree JM, Gerrits MA, Vanderschuren, LJ (1999) Opioids, reward and addiction: an encounter of biology, psychology, and medicine. Pharmacol Rev 51: 341–396

    Google Scholar 

  • Vela G, Ruiz-Gayo M, Fuentes JA (1995) Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically treated with morphine. Neuropharmacology 34: 665–668

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex 10: 318–325

    Article  PubMed  CAS  Google Scholar 

  • White FJ (1996) Synaptic regulation of mesocorticolimbic dopamine neurons. Annu Rev Neurosci 19: 405–436

    Article  PubMed  CAS  Google Scholar 

  • Wise RA (1996) Addictive drugs and brains timulation reward. Annu Rev Neurosci 19: 319–340

    Article  PubMed  CAS  Google Scholar 

  • Zimmer A, Valjent E, Konig M, Zimmer AM, Robledo P, Hahn H, Valverde O, Maldonado R (2001) Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice. J Neurosci 21: 9499–9505

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratori de Neurofarmacologia, Facultat de Ciènces de la Salut i de la Vida, Universitat Pompeu Fabra, C/Dr Aiguador 80, E-08003, Barcelona, Spain

    R. Maldonado

Authors
  1. R. Maldonado
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biological Psychiatry, Innsbruck University Clinics, Anichstrasse 35, A-6020, Innsbruck, Austria

    W. W. Fleischhacker

  2. MRC Cyclotron Unit, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    D. J. Brooks

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Wien

About this paper

Cite this paper

Maldonado, R. (2003). The neurobiology of addiction. In: Fleischhacker, W.W., Brooks, D.J. (eds) Addiction Mechanisms, Phenomenology and Treatment. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0541-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0541-2_1

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-01316-8

  • Online ISBN: 978-3-7091-0541-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation