title: The cannabinoid receptor antagonist SR 141716 attenuates overfeeding induced by systemic or intracranial morphine.
abstract: BACKGROUND
  Considerable interplay exists between the brain's opioid and cannabinoid systems. These systems are both involved in the control of appetite and research supports the notion that the opioid system modulates the role of the cannabinoid system on appetite. However, the ability of the cannabinoid system to modulate the opioid system's control over appetite has not been well studied.
  
  
  OBJECTIVE
  The present study examined the role of cannabinoid CB(1) receptors in the control of opioid-induced feeding, and sought to identify specific brain regions underlying this role.
  
  
  METHODS
  After being habituated to the test environment and injection procedure, sated rats were injected with the cannabinoid CB(1) receptor antagonist SR 141716 (0.03-3.0 mg/kg, IP). Thirty minutes later, morphine or its vehicle were administered systemically (2.5 mg/kg SC, experiments 1 and 2) or intracranially into the nucleus accumbens (nAcc, experiment 3) or paraventricular nucleus of the hypothalamus (PVN, experiment 4). Food intake and locomotor activity was then recorded for 120 min.
  
  
  RESULTS
  A significant increase in food intake was observed following systemic and intracranial (10 nmol) application of morphine in all experiments. SR 141716 suppressed systemic and intra-PVN morphine induced feeding (experiments 2 and 4), but did not attenuate food intake induced by intra-nAcc application of morphine (experiment 3).
  
  
  CONCLUSIONS
  Because SR 141716 had no effect on intra-nAcc morphine-stimulated feeding, it would appear that cannabinoid receptors do not modify opioid-mediated hedonic responses to food. Rather, we conclude that cannabinoid CB(1) receptor blockade may suppress opioid-induced feeding by stimulating the release of satiety-related peptides within the hypothalamus. Further, because SR 141716 did not block morphine induced locomotor activity, the observed effects on feeding do not appear to be due to a non-specific reduction in motivated behaviour.
authors.affiliation: School of Psychology, University of New England, Armidale, 2351 NSW, Australia.
authors.forename: Aaron N A
authors.initials: AN
authors.lastname: Verty
authors.forename: Malini E
authors.initials: ME
authors.lastname: Singh
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
authors.forename: Paul E
authors.initials: PE
authors.lastname: Mallet
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D005247:Feeding Behavior / Q000187:drug effects; D006963:Hyperphagia / Q000523:psychology*; D007267:Injections; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000819:agonists; D000077285:Rimonabant; D013238:Stereotaxic Techniques
chemical_list: D001067:Appetite Depressants; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D009294:Narcotics; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011957:Receptors, Opioid; D009020:Morphine; D000077285:Rimonabant