Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine.
Presatiated adult male Lister hooded rats received oral administration of the exogenous cannabinoid Delta-9-tetrahydrocannabinol (Delta(9)-THC; 1.0 mg/kg) in combination with subcutaneous injection of either the cannabinoid CB1 antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the CB2 antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the general opioid antagonist naloxone (0.1, 0.5, 1.0 or 5.0 mg/kg) or the 5-HT agonist dexfenfluramine (0.05, 0.1, 0.5, 1.0 or 5.0 mg/kg). Food (chow) intake was measured over 2 h from the onset of the dark period. Delta(9)-THC induced significant hyperphagia, which was attenuated by subanorectic doses of SR141716 and naloxone. Neither SR144528 nor dexfenfluramine affected Delta(9)-THC-induced feeding. These data confirm mediation of Delta(9)-THC hyperphagia by central-type CB1 receptors, and support a functional relationship between cannabinoid and opioid systems in relation to appetite regulation. Stimulation of CB1 receptors may promote feeding by actions on food reward rather than by inhibition of serotonergic satiety mechanisms.
Williams
Claire M
CM
Department of Psychology, University of Reading, PO Box 238, Earley Gate, Whiteknights, Reading RG6 6AL, UK.
Kirkham
Tim C
TC
D000818:Animals; D020372:Dexfenfluramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D006963:Hyperphagia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology; D000077285:Rimonabant; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
C469526:Cnr2 protein, rat; D009292:Narcotic Antagonists; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D017366:Serotonin Receptor Agonists; D009270:Naloxone; D013759:Dronabinol; D020372:Dexfenfluramine; D000077285:Rimonabant