Skip to main content
SpringerLink
Log in

CB1 cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Addictive drugs have a number of commonalities in animal behavioral models. They lower intracranial self-stimulation (ICSS) thresholds, support self-administration, and produce conditioned place preference (CPP). However, cannabinoids appear atypical as drugs of abuse, since there are controversial data in the literature concerning their reinforcing properties.

Objectives

The aim of the present study was to examine the effects of cannabinoids on brain reward using the rate–frequency curve shift paradigm of ICSS.

Methods

Male Sprague–Dawley rats were implanted with electrodes into the medial forebrain bundle (MFB). Rate–frequency functions were determined by logarithmically decreasing the number of cathodal pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After brain stimulation reward thresholds stabilized rats received intraperitoneal (IP) injections of the potent CB1 receptor agonists WIN 55,212-2 (graded doses 0.1, 0.3, 1 and 3 mg/kg), CP 55,940 (graded doses 10, 30, 56 and 100 μg/kg), or HU-210 (graded doses 10, 30, 100 μg/kg).

Results

With the exception of the highest dose of all cannabinoid agonists tested, which significantly increased the threshold frequency required for MFB ICSS, all other doses of the tested drugs did not affect ICSS thresholds. The CB1 receptor antagonist SR141716A reversed the actions of WIN 55,212-2 and CP 55,940, but not HU-210. However, the selective CB1 cannabinoid receptor antagonist AM 251 counteracted the effect of HU-210. Both CB1 receptor antagonists, at the doses used in the present study, did not affect reward thresholds by themselves.

Conclusions

The present results indicate that cannabinoid agonists do not exhibit reinforcing properties in the ICSS paradigm, but rather have an inhibitory influence on reward mechanisms. The results suggest that the anhedonic effects of cannabinoids are probably mediated by cannabinoid CB1 receptors.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adams IB, Martin BR (1996) Cannabis: pharmacology and toxicology in animals and humans. Addiction 91:1585–1614

    Article  CAS  PubMed  Google Scholar 

  • Ameri A (1999) The effects of cannabinoids on the brain. Prog Neurobiol 58:315–348

    Article  CAS  PubMed  Google Scholar 

  • Arnold JC, Hunt GE, McGregor IS (2001) Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats. Life Sci 70:97–108

    Article  CAS  PubMed  Google Scholar 

  • Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, Barth F, Calandra B, Pecceu F, Lupker J, Maffrand JP, Le Fur G, Casellas P (1997) A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 272(35):22330–22339

    Article  CAS  PubMed  Google Scholar 

  • Braida D, Pozzi M, Cavallini R, Sala M (2001a) Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system. Neuroscience 104:923–926

    Google Scholar 

  • Braida D, Pozzi M, Parolaro D, Sala M (2001b) 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  CAS  PubMed  Google Scholar 

  • Breivogel CS, Griffin G, Di Marzo V, Martin BR (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155–163

    CAS  PubMed  Google Scholar 

  • Chaperon F, Thiébot MH (1998) Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 13:243–281

    Google Scholar 

  • Chaperon F, Soubrié P, Puech AJ, Thiébot MH (1998) Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats. Psychopharmacology 135:324–332

    Article  CAS  PubMed  Google Scholar 

  • Cheer JF, Kendall DA, Marsden CA (2000) Cannabinoid receptors and reward in the rat: a conditioned place preference study. Psychopharmacology 151:25–30

    Article  CAS  PubMed  Google Scholar 

  • Compton DR, Gold LH, Ward SJ, Blster RL, Martin BR (1992) Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta-9-tetrahydrocannabinol. J Pharmacol Exp Ther 263:1118–1126

    CAS  PubMed  Google Scholar 

  • Corcoran ME, Amit Z (1974) Reluctance of rats to drink hashish suspensions: free choice and forced consumption and the effects of hypothalamic stimulation. Psychopharmacologia 352:129–147

    Article  Google Scholar 

  • Coulombe D, Miliaressis E (1987) Fitting intracranial self-stimulation data with growth models. Behav Neurosci 101:209–214

    Article  CAS  PubMed  Google Scholar 

  • Deroche-Gamonet V, Le Moal M, Piazza PV, Soubrié P (2001) SR 141716, a CB1 receptor antagonist, decreases the sensitivity to the reinforcing effects of electrical brain stimulation in rats. Psychopharmacology 157:254–259

    Article  CAS  PubMed  Google Scholar 

  • Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949

    CAS  PubMed  Google Scholar 

  • De Vry J, Jentzsch KR (2003) Intrinsic activity estimation of cannabinoid CB1 receptor ligands in a drug discrimination paradigm. Behav Pharmacol 14:471–476

    PubMed  Google Scholar 

  • De Vry J, Jentzsch KR (2004) Partial agonist-like profile of the cannabinoid receptor antagonist SR141716A in a food-reinforced operant paradigm. Behav Pharmacol 15:13–20

    Article  PubMed  Google Scholar 

  • Di Chiara G, Acquas E, Tanda G, Cadoni C (1993) Drugs of abuse: biochemical surrogates of specific aspects of natural reward? Biochem Soc Symp 59:65–81

    PubMed  Google Scholar 

  • Di Marzo V, Berrendero F, Bisogno T, Gonzalez S, Cavaliere P, Romero J, Cebeira M, Ramos JA, Fernandez-Ruiz JJ (2000) Enhancement of anandamide formation in the limbic forebrain and reduction of endocannabinoid contents in the striatum of delta9-tetrahydrocannabinol-tolerant rats. J Neurochem 74:1627–1635

    Article  PubMed  Google Scholar 

  • Elsmore TF, Fletcher GV (1972) Δ9-Tetrahydrocannabinol: aversive effects in rats at high doses. Science 171:911–912

    Google Scholar 

  • Fattore L, Cossu G, Martellotta CM, Fratta W (2001) Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats. Psychopharmacology 156:410–416

    Article  CAS  PubMed  Google Scholar 

  • Felder CC, Glass M (1998) Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 38:179–200

    Article  CAS  PubMed  Google Scholar 

  • Fibiger HC, Phillips AG (1986) Reward, motivation, cognition: psychobiology of the mesotelencephalic systems. In: Bloom FE (ed) Handbook of physiology, section I: the nervous system, vol IV. American Psysiological Society, Bethesda, pp 647–675

    Google Scholar 

  • Fouriezos G, Wise RA (1976) Pimozide-induced extinction of intracranial self-stimulation: response patterns rule out motor or performance deficits. Brain Res 103:377–380

    Article  CAS  PubMed  Google Scholar 

  • Fouriezos G, Hansson P, Wise RA (1978) Neuroleptic-induced attenuation of brain stimulation reward in rats. J Comp Physiol Psychol 92:661–671

    CAS  PubMed  Google Scholar 

  • Franklin KBJ (1978) Catecholamines and self-stimulation: reward and performance effects dissociated. Pharmacol Biochem Behav 9:813–820

    Article  CAS  PubMed  Google Scholar 

  • Gallistel CR, Freyd G (1987) Quantitative determination of the effects of catecholaminergic agonists and antagonists on the rewarding efficacy of brain stimulation. Pharmacol Biochem Behav 26:731–741

    Article  CAS  PubMed  Google Scholar 

  • Gallistel CR, Karras D (1984) Pimozide and amphetamine have opposing effects on the reward summation function. Pharmacol Biochem Behav 20:73–77

    Article  CAS  PubMed  Google Scholar 

  • Gardner EL, Vorel SR (1998) Cannabinoid transmission and reward-related events. Neurobiol Dis 5:502–533

    Article  CAS  PubMed  Google Scholar 

  • Gardner EL, Paredes W, Smith D, Donner A, Milling C, Cohen D, Morrison D (1988) Facilitation of brain stimulation reward by Δ9-tetrahydrocannabinol. Psychopharmacology 96:142–144

    CAS  PubMed  Google Scholar 

  • Gatley SJ, Gifford AN, Volkow ND, Lan R, Makriyannis A (1996) 123I-labeled AM251: a radioiodinated ligand which binds in vivo to mouse brain cannabinoid CB1 receptors. Eur J Pharmacol 307:331–338

    Article  CAS  PubMed  Google Scholar 

  • Grotenhermen F (2004) Pharmacology of cannabinoids. Neuroendocrinol Lett 25(1/2):14–23

    Article  CAS  PubMed  Google Scholar 

  • Haller J, Bakos N, Szirmay M, Ledent C, Freund TF (2002) The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety. Eur J Neurosci 16(7):1395–1398

    Article  CAS  PubMed  Google Scholar 

  • Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98:3662–3665

    Article  CAS  PubMed  Google Scholar 

  • Harris RT, Waters W, McLendon D (1974) Evaluation of reinforcing capability of DELTA 9-THC in rhesus monkeys. Psychopharmacologia 37:23–39

    CAS  PubMed  Google Scholar 

  • Harrison AA, Liem YTB, Markou A (2001) Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats. Neuropsychopharmacology 25:55–71

    Article  CAS  PubMed  Google Scholar 

  • Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis L, Fezza F, Tognetto M, Petros TJ, Krey JF, Chu CJ, Miller JD, Davies SN, Geppetti P, Walker JM, Di Marzo V (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99:8400–8405

    Article  CAS  PubMed  Google Scholar 

  • Hunt T, Amit Z (1987) Conditioned taste aversion induced by self-administered drugs: paradox revisited. Neurosci Biobehav Rev 11:107–130

    CAS  PubMed  Google Scholar 

  • Iversen L (2003) Cannabis and the brain. Brain 126:1252–1270

    Article  PubMed  Google Scholar 

  • Järbe TUC, DiPatrizio NV, Li C, Makriyiannis A (2003a) The cannabinoid receptor antagonist SR-141716A does not readily antagonize open-field effects induced by the cannabinoid receptor agonist (R)-methanandamide in rats. Pharmacol Biochem Behav 75:809–821

    Article  PubMed  Google Scholar 

  • Järbe TUC, Lamb RJ, Liu Q, Makriyiannis A (2003b) (R)-methanandamide and Δ9-tetrahydrocannabinol-induced operant rate decreases in rats are not readily antagonized by SR-141716A. Eur J Pharmacol 466:121–127

    Article  PubMed  Google Scholar 

  • Justinova Z, Tanda G, Redhi GH, Goldberg SR (2003) Self-administration of Δ9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology 169:135–140

    Article  CAS  PubMed  Google Scholar 

  • Kucharski LT, Williams JE, Kornetsky C (1983) The effects of levonantradol on rewarding brain stimulation thresholds in the rat. Pharmacol Biochem Behav 19:149–151

    Article  CAS  PubMed  Google Scholar 

  • Landsman RS, Burkey TH, Consroe P, Roeske WR, Yamamura HI (1997) SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur J Pharmacol 334:R1–R2

    Article  CAS  PubMed  Google Scholar 

  • Leite JL, Carlini EA (1974) Failure to obtain “cannabis directed behavior” and abstinence syndrome in rats chronically treated with cannabis sativa extracts. Psychopharmacologia 36:133–145

    CAS  PubMed  Google Scholar 

  • Lepore M, Vorel SR, Lowinson J, Gardner EL (1995) Conditioned place preference induced by Δ9-tetrahydrocannabinol: comparison with cocaine, morphine and food reward. Life Sci 56:2073–2080

    Article  CAS  PubMed  Google Scholar 

  • Lepore M, Liu X, Savage V, Matalon D, Gardner EL (1996) Genetic differences in Δ9-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 58:365–372

    Article  Google Scholar 

  • Liebman JM (1983) Discriminating between reward and performance: a critical review of intracranial self-stimulation methodology. Neurosci Biobehav Rev 7:45–72

    Article  CAS  PubMed  Google Scholar 

  • Maldonado-Irizarry CS, Stellar JR, Kelley AE (1994) Effects of cocaine and GBR-12909 on brain stimulation reward. Pharmacol Biochem Behav 48:915–920

    Article  CAS  PubMed  Google Scholar 

  • Mallet PE, Benninger RJ (1998) Δ9-tetrahydrocannabinol, but not the endogenous cannabinoid receptor ligand anandamide, produces conditioned place avoidance. Life Sci 62:2431–2439

    Article  CAS  PubMed  Google Scholar 

  • Mansbach RS, Nicholson KL, Martin BR, Balster RL (1994) Failure of Δ9-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys. Behav Pharmacol 5:210–225

    PubMed  Google Scholar 

  • Markou A, Koob GF (1992) Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations. Physiol Behav 51:111–119

    Article  CAS  PubMed  Google Scholar 

  • Markou A, Koob GF (1993) Intracranial self-stimulation thresholds are a measure of reward. In: Saghal A (ed) Behavioral neuroscience: a practical approach, vol II. IRL, Oxford, pp 93–115

    Google Scholar 

  • Martellotta MC, Cossu G, Fattore L, Gessa GL, Fratta W (1998) Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice. Neuroscience 85:327–330

    Google Scholar 

  • Martin BR, Compton DR, Thomas BF, Prescott WR, Little PJ, Razdan RK, Johnson MR, Melvin LS, Mechoulam R, Ward SJ (1991) Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 40:471–478

    Article  CAS  PubMed  Google Scholar 

  • Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

    Article  CAS  PubMed  Google Scholar 

  • McGregor IS, Issakidis CN, Prior G (1996) Aversive effects of the synthetic cannabinoid CP 55,940 in rats. Pharmacol Biochem Behav 53:657–664

    Article  CAS  PubMed  Google Scholar 

  • Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

    Article  CAS  PubMed  Google Scholar 

  • Miliaressis E, Rompré P-P (1987) Effects of concomitant motor reactions on the measurement of rewarding efficacy of brain stimulation. Behav Neurosci 101:827–831

    Article  CAS  PubMed  Google Scholar 

  • Miliaressis E, Rompré PP, Laviolette P, Philippe L, Coulombe D (1986) The curve-shift paradigm in self-stimulation. Physiol Behav 37:85–91

    Article  CAS  PubMed  Google Scholar 

  • Mo FM, Offertáler L, Kunos G (2004) Atypical cannabinoid stimulates endothelial cell migration via a Gi/Go-coupled receptor distinct from CB1, CB2 or EDG-1. Eur J Pharmacol 489:21–27

    Article  CAS  PubMed  Google Scholar 

  • Munro S, Thomas KL, Abu SM (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

    Article  CAS  PubMed  Google Scholar 

  • Palmer SL, Thakur GA, Makriyiannis A (2002) Cannabinergic ligands. Chem Phys Lipids 121:3–19

    Article  CAS  PubMed  Google Scholar 

  • Panagis G, Spyraki C (1996) Neuropharmacological evidence for the role of dopamine in ventral pallidum self-stimulation. Psychopharmacology 123:280–288

    CAS  PubMed  Google Scholar 

  • Panagis G, Kastellakis A, Spyraki C, Nomikos G (2000) Effects of methyllycaconitine (MLA), an α7 nicotinic receptor antagonist, on nicotine- and cocaine-induced potentiation of brain stimulation reward. Psychopharmacology 149:388–396

    Article  CAS  PubMed  Google Scholar 

  • Parker LA, Gillies T (1995) THC-induced place and taste aversions in Lewis and Sprague–Dawley rats. Behav Neurosci 109:71–78

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic, San Diego

    Google Scholar 

  • Pertwee RG (1999) Pharmacology of cannabinoid receptor ligands. Curr Med Chem 6:635–664

    CAS  PubMed  Google Scholar 

  • Porter AC, Felder CC (2001) The endocannabinoid nervous system: unique opportunities for therapeutic intervention. Pharmacol Ther 90:45–60

    Article  CAS  PubMed  Google Scholar 

  • Porter AC, Sauer JM, Knierman MD, Becker GW, Berna MJ, Bao J, Nomikos GG, Carter P, Bymaster FP, Leese AB, Felder CC (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301:1020–1024

    Article  CAS  PubMed  Google Scholar 

  • Ranaldi R, Beninger RJ (1994) The effects of systemic and intracerebral injections of D1 and D2 agonists on brain stimulation reward. Brain Res 651:283–292

    Article  CAS  PubMed  Google Scholar 

  • Rinaldi-Carmona M, Barth F, Héaulme M, Shire D, Calandra B, Congry C, Martinez S, Maruani J, Néliat G, Caput D et al. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240–244

    Article  CAS  PubMed  Google Scholar 

  • Robinson L, Hinder L, Pertwee RG, Riedel G (2003) Effects of Δ9-THC and WIN 55,212-2 on place preference in the water maze in rats. Psychopharmacology 166:40–50

    CAS  PubMed  Google Scholar 

  • Romero J, Lastres-Becker I, De Miguel R, Berrendero F, Ramos, JA, Fernández-Ruiz J (2002) The endogenous cannabinoid system and the basal ganglia: biochemical, pharmacological, and therapeutic aspects. Pharmacol Ther 95:137–152

    Article  CAS  PubMed  Google Scholar 

  • Rompré PP, Wise RA (1989) Opioid-neuroleptic interaction in brainstem self-stimulation. Brain Res 477:144–151

    Article  PubMed  Google Scholar 

  • Russo EB, McPartland JM (1993) Cannabis is more than simply Δ9-tetrahydrocannabinol. Psychopharmacology 165:431–432

    Google Scholar 

  • Sañudo-Pena MC, Tsou K, Delay ER, Hohman AG, Force M, Walker M (1997) Endogenous cannabinoids as an aversive or counter-rewarding system in the rat. Neurosci Lett 223:125–128

    Article  PubMed  Google Scholar 

  • Solinas M, Panlilio LV, Antoniou K, Pappas LA, Goldberg SR (2003) The cannabinoid CB1 antagonist N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR-141716A) differentially alters the reinforcing effects of heroin under continuous reinforcement, fixed ratio, and progressive ratio schedules of drug self-administration in rats. J Pharmacol Exp Ther 306(1):93–102

    Article  CAS  PubMed  Google Scholar 

  • Stark P, Dews PB (1980) Cannabinoids: behavioral effects. J Pharmacol Exp Ther 214:124–130

    CAS  PubMed  Google Scholar 

  • Stellar JR, Rice MB (1989) Pharmacological basis of intracranial self-stimulation reward. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford Science, Oxford, pp 14–65

    Google Scholar 

  • Takahashi RN, Singer G (1979) Self-administration of delta-9-tetrahydrocannabinol by rats. Pharmacol Biochem Behav 11:737–740

    Article  CAS  PubMed  Google Scholar 

  • Tanda G, Goldberg SR (2003) Cannabinoids: reward, dependence, and underlying neurochemical mechanisms—a review of recent preclinical data. Psychopharmacology 169:115–134

    Article  CAS  PubMed  Google Scholar 

  • Tanda G, Munzar P, Goldberg SR (2000) Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci 3:1073–1074

    Article  CAS  PubMed  Google Scholar 

  • Valjent E, Maldonado R (2000) A behavioral model to reveal place preference to Δ9-tetrahydrocannabinol in mice. Psychopharmacology 147:436–438

    Article  CAS  PubMed  Google Scholar 

  • Van Ree JM, Slangen J, de Wied D (1978) Intravenous self-administration of drugs in rats. J Pharmacol Exp Ther 20:547–557

    Google Scholar 

  • Vlachou S, Nomikos GG, Panagis G (2003) WIN 55,212-2 decreases the reinforcing actions of cocaine through CB1 cannabinoid receptor stimulation. Behav Brain Res 141:215–222

    Article  CAS  PubMed  Google Scholar 

  • Wasserman EM, Gomita Y, Gallistel CR (1982) Pimozide blocks reinforcement but not priming from MFB stimulation in the rat. Pharmacol Biochem Behav 17:783–787

    Article  CAS  PubMed  Google Scholar 

  • Wise RA (1980) Action of drugs of abuse on brain reward systems. Pharmacol Biochem Behav 13(1):213–223

    PubMed  Google Scholar 

  • Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–87

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Wise RA (1998) Drug-activation of brain reward pathways. Drug Alcohol Depend 51:13–22

    Article  CAS  PubMed  Google Scholar 

  • Wise RA, Rompré PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225

    Article  CAS  PubMed  Google Scholar 

  • Wise R, Marcangione C, Bauco P (1998) Blockade of the reward-potentiating effect of nicotine on lateral hypothalamic brain stimulation by chlorisondamine. Synapse 29:72–79

    Article  CAS  PubMed  Google Scholar 

  • Zimmer A, Zimmer AM, Hobmann AG, Henkenham M, Bonner TI (1999) Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96:5780–5785

    Article  CAS  PubMed  Google Scholar 

  • Zygmunt PM, Andersson DA, Högestätt ED (2002) Δ9-Tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism. J Neurosci 22:4720–4727

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by a grant from the General Secreteriat of Research and Technology of Greece—European Commission (EPAN—YB/60). Vlachou Styliani was supported by a scholarship from PROPONTIS Foundation. We thank A. Galanopoulos and F. Stamatopoulou for their assistance in the conduction of some experiments.

Author information

Authors and Affiliations

  1. Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, 74100, Rethymnon, Crete, Greece

    Styliani Vlachou & George Panagis

  2. Neuroscience Research, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46285-0510, USA

    George G. Nomikos

Authors
  1. Styliani Vlachou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George G. Nomikos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Panagis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George Panagis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vlachou, S., Nomikos, G.G. & Panagis, G. CB1 cannabinoid receptor agonists increase intracranial self-stimulation thresholds in the rat. Psychopharmacology 179, 498–508 (2005). https://doi.org/10.1007/s00213-004-2050-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-004-2050-0

Keywords

Search

Navigation