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 mu-g/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-mu-g) or median (0.5-mu-g) raphe. Microinjecting 2-mu-g 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-mu-g) injected into this site blocked the feeding responses to intra-raphe 8-OH-DPAT. Examination of the effects of naloxone and methyl-naltrexone in food-deprived rats ruled out intrinsic anorectic actions of these drugs as an explanation for the antagonism of 8-OH-DPAT-induced feeding. The results may indicate that reduced 5-HT function increases opiate activity in the nucleus accumbens. Alternatively opiate antagonists may prevent the indirect facilitation of dopamine activity resulting from a reduction in 5-HT neurotransmission. Opiate and dopamine systems in the nucleus accumbens play a major role in reward processes. Since opiate and dopamine antagonists reverse 8-OH-DPAT-induced feeding the possible role of reward mechanisms in mediating the effect of 8-OH-DPAT is discussed.