Dorsal raphe microinjection of 5-HT and indirect 5-HT agonists induces feeding in rats.
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.
Fletcher
P J
PJ
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Davies
M
M
D000818:Animals; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D015031:Zimeldine / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D011985:Receptors, Serotonin; D005277:Fenfluramine; D012701:Serotonin; D015031:Zimeldine; C038213:brofaromine