zimeldine and brofaromine

Previous work has shown that 5-hydroxytryptamine (5-HT) receptor agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reduce 5-HT neurotransmission and induce feeding in rats. The effects of 8-OH-DPAT appear to be mediated in part in the dorsal raphe nucleus by serotonergic somatodendritic autoreceptors which normally regulate impulse flow in 5-HT dorsal raphe neurons. The present experiments sought to examine whether suppression of dorsal raphe serotonergic neural activity induced by exogenously applied, or endogenously released 5-HT would increase feeding. Free-feeding rats were microinjected in the dorsal raphe with 5-HT, the 5-HT releasing compound d-fenfluramine, the 5-HT re-uptake inhibitor zimelidine, or the type-A monoamine oxidase inhibitor brofaromine. Dose dependent increases in food intake over a 1 h period were found following treatment with 5-HT and the three indirectly acting compounds. Thus, increased serotonergic activity within the dorsal raphe increases feeding, presumably by inhibiting the activity of dorsal raphe 5-HT neurons. In addition the effects of 5-HT were blocked by pretreatment with haloperidol, indicating the involvement of a dopaminergic mechanism in mediating the effects of feeding of a suppression in dorsal raphe 5-HT neural activity. The results are discussed in terms of the general role which serotonergic neurons arising from the dorsal raphe may play in behavioural inhibition.

Topics: Animals; Feeding Behavior; Fenfluramine; Male; Microinjections; Monoamine Oxidase Inhibitors; Piperidines; Raphe Nuclei; Rats; Receptors, Serotonin; Serotonin; Zimeldine