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 within the nucleus accumbens results in marked hyperphagia, perhaps reflecting enhancement of taste palatability. Rats that have received multiple morphine treatments also increase feeding in response to environmental stimuli that have been associated with the morphine injections. The present investigation further examined this phenomenon. In Experiment 1, it was shown that induction of conditioned feeding was dose-dependent; significant conditioned feeding was obtained with repeated (n = 5) intra-accumbens injections of 5 or 10 microg/microl morphine but not with saline or 1 microg. The conditioned feeding response was blocked by systemic naltrexone (5 mg/kg). In the second experiment, co-treatment with either a D-1 (SCH 23390, 0.1 mg/kg) or D-2 (haloperidol, 0.25 mg/kg) antagonist did not block the development of conditioned feeding, nor did these drugs block morphine-induced feeding. In Experiment 3, it was found that systemic naltrexone blocked the expression of conditioned feeding (confirming Experiment 1), as did SCH-23390, whereas haloperidol did not affect expression of conditioned feeding. In the fourth experiment, we observed that significant conditioned feeding was induced with repeated treatment with the selective mu agonist D-Ala2, NMe-phe4, Glyol5-enkephalin (DAMGO, 2.5 microg), but not with the delta agonist D-Pen2,5-enkephalin (DPEN, 3.1 microg). 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 opioid-induced conditioned feeding depends on mu opiate receptor stimulation, but not dopamine receptor stimulation. Its expression, however, involves both opiate and D-1 receptor activation. These findings are considered in terms of putative neural mechanisms governing conditioned meal initiation, and implications for compulsive eating and bulimia are also discussed.
Kelley
A E
AE
Department of Psychiatry, University of Wisconsin-Madison Medical School, Madison, WI 53705, USA.
Bakshi
V P
VP
Fleming
S
S
Holahan
M R
MR
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D009020:Morphine