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The cannabinoid CB1 receptor antagonist SR141716A reduces appetitive and consummatory responses for food

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Abstract

Rationale

The CB1 receptor antagonist SR141716A reduces food intake in rats. This effect is likely to depend on modulation of reward related processes.

Objective

To investigate the effects of SR141716A on responding for food under a second order instrumental task in which responding and consumption of food can be separated, and on Pavlovian responding for a stimulus predictive of food reward.

Methods

Instrumental responding and pellet consumption following administration of SR141716A (0–3 mg/kg) were recorded under an FI5 min FR5(5:S) operant schedule that incorporates both a 5 min initial appetitive phase and a 25 min consummatory phase. We compared the drug-induced change in responding to that recorded following a reduction in motivational state induced by pre-feeding. In a second experiment we assessed the effects of SR141716A (0–3 mg/kg) on Pavlovian approach behaviour for a stimulus (lever) associated with food reward (CS+) and a neutral stimulus (lever) not associated with reward (CS−).

Results

SR141716A reduced pellet consumption and instrumental responding during both the appetitive and consummatory phases of the second order schedule. Pre-feeding had a similar effect on responding during the appetitive phase, suggesting an effect on incentive motivation. SR141716A also blocked an enhancement of responding that occurred during the consummatory phase in pre-fed animals. SR141716A and pre-feeding had no effect on responding in the Pavlovian autoshaping paradigm.

Conclusions

SR141716A impacts on motivational processes in both the appetitive and consummatory phases of feeding behaviour.

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References

  • Aceto MD, Scates SM, Radzan RK, Martin BR (1998) Anandamide, an endogenous cannabinoid, has a very low physical dependence potential. J Exp Ther 287:598–605

    CAS  Google Scholar 

  • Balleine B (1992) Instrumental performance following a shift in primary motivation depends on incentive learning. J Exp Psychol 18:236–250

    CAS  Google Scholar 

  • Berry EM, Mechoulam R (2002) Tetrahydrocannabinol and endocannabinoids in feeding and appetite. Pharmacol Ther 95:185–190

    Article  CAS  PubMed  Google Scholar 

  • Bindra D (1974) Neuropsychological interpretation of the effects of drive and incentive-motivation on general activity and instrumental behaviour. Psychol Rev 75:1–22

    Google Scholar 

  • Blundell P, Hall G, Killcross S (2003) Preserved sensitivity to outcome value after lesions of the basolateral amygdala. J Neurosci 23:7702–7709

    CAS  PubMed  Google Scholar 

  • Chaperon F, Soubrie P, Puech AJ, Theibot 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 

  • Clifton PG, Burton MJ, Sharp C (1987) Rapid loss of stimulus-specific satiety after consumption of a second food. Appetite 9:149–156

    CAS  PubMed  Google Scholar 

  • Deroche-Gamonet V, Le Moal M, Piazza PV, Soubrie P (2001) SR141716, 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 

  • De Vries TJ, Shaham Y, Homberg JR, Crombag H, Schuurman K, Dieben J, Vanderschuren LJ, Schoffelmeer AN (2001) A cannabinoid mechanism in relapse to cocaine seeking. Nat Med 7:1151–1154

    Article  PubMed  Google Scholar 

  • De Vries TJ, Homberg JR, Binnekade R, Raaso H, Schoffelmeer AN (2003) Cannabinoid modulation of the reinforcing and motivational properties of heroin and heroin-associated cues in rats. Psychopharmacology 168:164–169

    Article  PubMed  Google Scholar 

  • Dickinson A, Balleine B (1994) Motivational control of goal-directed action. Anim Learn Behav 22:1–18

    Google Scholar 

  • Di Ciano P, Cardinal RN, Cowell RA, Little SJ, Everitt BJ (2001) Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of Pavlovian approach behavior. J Neurosci 21:9471–9477

    PubMed  Google Scholar 

  • Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jaral Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G (2001) Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410:822–825

    Article  PubMed  Google Scholar 

  • Fattore L, Spano MS, Cossu G, Deiana S, Fratta W (2003) Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats. Eur J Neurosci 17:1723–1726

    CAS  PubMed  Google Scholar 

  • Freedland CS, Poston JS, Porrino LJ (2000) Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding. Pharmacol Biochem Behav 67:265–270

    Article  CAS  PubMed  Google Scholar 

  • Freedland CS, Sharpe AL, Samson HH, Porrino LJ (2001) Effects of SR141716A on ethanol and sucrose self administration. Alcohol Clin Exp Res 25:277–282

    Article  CAS  PubMed  Google Scholar 

  • Gallate JE, McGregor IS (1999) The motivation for beer in rats: effects of ritanserin, naloxone and SR141716. Psychopharmacology 142:302–308

    Article  CAS  PubMed  Google Scholar 

  • Gardner EL (2002) Addictive potential of cannabinoids: the underlying neurobiology. Chem Phys Lipids 121:267–290

    Article  CAS  PubMed  Google Scholar 

  • Halford JC, Lawton CL, Blundell JE (1997) The 5-HT2 receptor agonist MK-212 reduces food intake and increases resting but prevents the behavioural satiety sequence. Pharmacol Biochem Behav 56:41–46

    Article  CAS  PubMed  Google Scholar 

  • Hatfield T, Han J, Conley M, Gallagher M, Holland M (1996) Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects. J Neurosci 16:5256–5265

    CAS  PubMed  Google Scholar 

  • Higgs S, Williams CM, Kirkham TC (2003) Cannabinoid influences on palatability: microstructural analysis of sucrose drinking after Δ9-THC, anandamide, 2-arachidonoyl glycerol and SR141716. Psychopharmacology 165:370–377

    CAS  PubMed  Google Scholar 

  • Holland PC, Straub JJ (1979) Differential effects of two ways of devaluing the unconditioned stimulus after Pavlovian appetitive conditioning. J Exp Psychol Anim Behav Proc 5:65–78

    Article  CAS  PubMed  Google Scholar 

  • Ishii Y, Blundell JE, Halford JC, Rodgers RJ (2003) Effects of systematic variation in presatiation and fasting on behavioural satiety sequence in male rats. Physiol Behav 79:227–238

    Article  CAS  PubMed  Google Scholar 

  • Jamshidi N, Taylor DA (2001) Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br J Pharmacol 134:1151–1154

    CAS  PubMed  Google Scholar 

  • Kirkham TC, Williams CM (1998) The cannabinoid receptor antagonist SR141716A fails to suppress sucrose sham feeding. J Psychopharmacol 12(Suppl A):37

    Google Scholar 

  • Kirkham TC, Williams CM (2001a) Endogenous cannabinoids and appetite. Nutr Res Rev 14:65–86

    CAS  Google Scholar 

  • Kirkham TC, Williams CM (2001b) Synergistic effects of opioid and cannabinoid antagonists on food intake. Psychopharmacology 153:267–270

    Article  CAS  PubMed  Google Scholar 

  • 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 136:550–557

    CAS  PubMed  Google Scholar 

  • Kitchener SJ, Dourish CT (1994) An examination of the behavioural specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats. Psychopharmacology 113:369–377

    CAS  PubMed  Google Scholar 

  • Ravinet Trillou C, Arnone M, Delgorge C, Gonaalons N, Keane P, Maffrand J-P, Soubrie P (2003) Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 284:R345–R353

    PubMed  Google Scholar 

  • Rowland NE, Mukherjee M, Robertson K (2001) Effects of the cannabinoid receptor antagonist SR141716, alone and in combination with dexfenfluramine or naloxone, on food intake in rats. Psychopharmacologia 159:111–116

    Article  CAS  Google Scholar 

  • Rubino T, Patrini G, Massi P, Fuzio D, Vigano D, Giagnoni G, Parolaro D (1998) Cannabinoid-precipitated withdrawal: a time-course study of the behavioural aspect and its correlation with cannabinoid receptors and G protein expression. J Pharmacol Exp Ther 285:813–819

    CAS  PubMed  Google Scholar 

  • Schindler CW, Panlilio LV, Goldberg SR (2002) Second-order schedules of drug self-administration in animals. Psychopharmacology 163:327–344

    Article  CAS  PubMed  Google Scholar 

  • Toates FM (1981) The control of ingestive behaviour by internal and external stimuli—a theoretical review. Appetite 2:35–50

    CAS  PubMed  Google Scholar 

  • Toates FM (1986) Motivational systems. Cambridge University Press, Cambridge

    Google Scholar 

  • Treit D, Spetch ML, Deutsch JA (1983) Variety in the flavour of food enhances eating in the rat: a controlled demonstration. Physiol Behav 30:207–211

    Article  CAS  PubMed  Google Scholar 

  • Vickers SP, Webster LJ, Wyatt A, Dourish CT, Kennett GA (2003) Preferential effects of the cannabinoid CB1 receptor antagonist SR141716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats. Psychopharmacology 167:103–111

    CAS  PubMed  Google Scholar 

  • Wiepkema PR (1971) Positive feedbacks at work during feeding. Behaviour 39:266–273

    CAS  PubMed  Google Scholar 

  • Williams CM, Kirkham TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology 143:315–317

    Article  CAS  PubMed  Google Scholar 

  • Williams CM, Kirkham TC (2002) Reversal of Δ9-THC hyperphagia by SR141716 and naloxone but not by dexfenfluramine. Pharmacol Biochem Behav 71:341–348

    Article  PubMed  Google Scholar 

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Acknowledgement

Z.T.-J. was supported by a MRC Industrial Collaborative Studentship with Vernalis Research Ltd.

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Correspondence to Peter G. Clifton.

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Thornton-Jones, Z.D., Vickers, S.P. & Clifton, P.G. The cannabinoid CB1 receptor antagonist SR141716A reduces appetitive and consummatory responses for food. Psychopharmacology 179, 452–460 (2005). https://doi.org/10.1007/s00213-004-2047-8

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  • DOI: https://doi.org/10.1007/s00213-004-2047-8

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