Fletcher P J, Coscina D V
Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Pharmacol Biochem Behav. 1993 Oct;46(2):487-91. doi: 10.1016/0091-3057(93)90385-7.
The selective 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) activates raphe somatodendritic autoreceptors, leading to an inhibition of 5-HT neuronal activity and reduced synthesis and release of 5-HT in forebrain terminal areas. One behavioural consequence of this is increased feeding in satiated rats. Because injections of 5-HT agonists into the medial hypothalamus suppress feeding, it has been proposed that 8-OH-DPAT-induced feeding may involve a reduction of 5-HT release within this area. This hypothesis was tested by examining the ability of 5-HT injected into the medial hypothalamus to reverse the feeding-stimulant action of 8-OH-DPAT following injection into the dorsal raphe or median raphe. Two groups of rats, maintained with free access to food at all times, were used. Each was prepared with two cannulae, one aimed at the paraventricular nucleus (PVN) of the medial hypothalamus and the other at either the dorsal raphe nucleus or median raphe nucleus. Food intake over the next hour was increased following dorsal raphe or median raphe injections of 8-OH-DPAT (1 and 0.5 microgram, respectively). These effects were not blocked by injections of 7.5 or 15 micrograms 5-HT into the PVN. However, 15 micrograms 5-HT did attenuate the feeding-stimulant action of 10 micrograms norepinephrine injected into the PVN. These results do not support the hypothesis that a reduction in 5-HT release within the medial hypothalamus is responsible for the feeding-stimulant action of 8-OH-DPAT.