Opiate antagonists inhibit feeding induced by 8-OH-DPAT: possible mediation in the nucleus accumbens.
Previous work has shown that the 5-hydroxytryptamine (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits a variety of behaviours, including feeding in rats. These effects are accompanied by reduced 5-HT neurotransmission resulting from activation of somatodendritic 5-HT receptors located in the midbrain raphe nuclei. Dopamine antagonists injected either peripherally or into the nucleus accumbens reverse 8-OH-DPAT-induced feeding. Thus a facilitation of dopamine activity, secondary to reduced 5-HT activity, may be involved in mediating 8-OH-DPAT-induced feeding. Opiate antagonists have been shown previously to reduce several dopamine-dependent behaviours including feeding induced by dopaminergic drugs, tail pinch and electrical brain stimulation. Therefore experiments were conducted to assess the effects of opiate antagonists on feeding induced by peripheral, and raphe injection of 8-OH-DPAT in free-feeding rats. Following SC injection naloxone (0.1-10 mg/kg) dose-dependently reduced the feeding response induced by 100 micrograms/kg 8-OH-DPAT (SC). The lowest effective dose of naloxone was 1 mg/kg. This dose of naloxone also suppressed feeding induced by 8-OH-DPAT injected into either the dorsal (1 microgram) or median (0.5 micrograms) raphe. Microinjecting 2 micrograms naloxone together with 8-OH-DPAT into either of these sites failed to prevent the increased feeding. These results indicate that the effects of naloxone are mediated at sites distal to the raphe nuclei. One possible site may be the nucleus accumbens, since methyl-naltrexone (0.3, 1 or 3 micrograms) injected into this site blocked the feeding responses to intra-raphe 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Fletcher
P J
PJ
Clarke Institute of Psychiatry, Section of Biopsychology, Toronto, Ont., Canada.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004435:Eating / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology*; D000644:Quaternary Ammonium Compounds; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; D013764:Tetrahydronaphthalenes; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin