A pharmacological analysis of the substrates underlying conditioned feeding induced by repeated opioid stimulation of the nucleus accumbens

It has previously been demonstrated that stimulation of opiate receptors wi thin the nucleus accumbens results in marked hyperphagia, perhaps reflectin g enhancement of taste palatability. Rats that have received multiple morph ine treatments also increase feeding in response to environmental stimuli t hat have been associated with the morphine injections. The present investig ation further examined this phenomenon. In Experiment I, if was shown that induction of conditioned feeding was dose-dependent; significant conditione d feeding was obtained with repeated (n = 5) intra-accumbers injections of 5 or 10 mu g/ul morphine but not with saline or 1 mu g. The conditioned fee ding response was blocked by systemic naltrexone (5 mg/kg). In the second e xperiment, co-treatment with either a D-I (SCH 23390, 0.1 mg/kg) or D-2 (ha loperidol, 0.25 mg/kg) antagonist did not block the development of conditio ned feeding, nor did these drugs block morphine-induced feeding. In Experim ent 3, it was found that systemic naltrexone blocked the expression of cond itioned feeding (confirming Experiment 1), as did SCH-23390, whereas halope ridol did not affect expression of conditioned feeding. In the fourth exper iment, we observed that significant conditioned feeding was induced with re peated treatment with the selective mu agonist D-Ala2, NMe-phe4, Glyol5-enk ephalin (DAMGO, 2.5 mu g), but not with the delta agonist D-Pen2,5-enkephal in (DPEN, 3.2 mu g). The final experiment tested the diurnal variability of the expression of conditioned feeding, and it was found that the magnitude of the effect depended on time of day. In summary, the development of opio id-induced conditioned feeding depends on mu opiate receptor stimulation, b ut not dopamine receptor stimulation. Its expression, however, involves bot h opiate and D-1 receptor activation. These findings are considered in term s of putative neural mechanisms governing conditioned meal initiation, and implications for compulsive eating and bulimia are also discussed. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.