Dopamine receptor blockade in nucleus accumbens or caudate nucleus differentially affects feeding induced by 8-OH-DPAT injected into dorsal or median raphe

Abstract

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 a reduction in 5-HT neurotransmission resulting from activation of somatodendritic 5-HT receptors located in the midbrain raphe nuclei. Previous work showing that dopamine receptor antagonists attenuate 8-OH-DPAT-induced feeding indicates that a facilitation of dopamine activity, secondary to reduced 5-HT activity, is involved in the expression of this effect. Microinjection studies were conducted to explore further the nature of this 5-HT-dopamine interaction. Injection of 8-OH-DPAT (0.125–2 μg) into either dorsal or median raphe induced dose-dependent increases in 1 h food intake in non-deprived rats. Pretreatment with haloperidol (0.05 and 0.1 mg/kg s.c.) attenuated the effect induced by median raphe 8-OH-DPAT (0.5 μg) complementing previous results with dorsal raphe 8-OH-DPAT. The feeding resulting from dorsal raphe (1 μg) or median raphe (0.5 μg) 8-OH-DPAT was attenuated by α-flupenthixol (1.25 and 2.5 μg) injected into the nucleus accumbens. α-Flupenthixol in either the dorsolateral or ventrolateral aspects of the caudate nucleus attenuated also the feeding response to dorsal raphe, but not median raphe, 8-OH-DPAT. However, α-flupenthixol in the dorsomedial caudate failed to alter feeding resulting from dorsal raphe 8-OH-DPAT. The results confirm the involvement of dopamine in mediating the effects on feeding of 8-OH-DPAT and suggest that overlapping but different mechanisms are involved in the expression of the feeding resulting from dorsal and median raphe injection of 8-OH-DPAT. Thus, while the nucleus accumbens appears to be involved in both effects, the caudate nucleus is involved only in the effect derived from the dorsal raphe. The nucleus accumbens has been implicated in reward processes, whereas dopamine in the lateral caudate appears to facilitate sensorimotor integration. It is possible that these processes may underlie 8-OH-DPAT feeding. In a broader context these results may have important implications for understanding the diversity of motivated behaviours which can be elicited by 8-OH-DPAT and a reduction in 5-HT function.