tropisetron and 5-methylurapidil

Previously, we have shown that serotonin (5-HT) can inhibit, excite, or biphasically inhibit and excite individual neurons of the ventromedial nucleus (VMN) in hypothalamic slices from female rats. In the present study, similar in vitro methods were used to further characterize VMN neurons responsive to 5-HT, and to identify the receptor subtypes involved in mediating these 5-HT actions. Results from a dose-response experiment indicate that increasing the dose of 5-HT can transform an inhibitory response into a biphasic or even an excitatory response. This indicates that modulation of 5-HT release in the VMN could alter the net response of the VMN to this transmitter. By comparing the actions of 5-HT with the effects of selective agonists and antagonists, the inhibitory action was found to be mediated predominantly, if not exclusively, by 5-HT1A receptors, while the excitatory action was mediated predominantly or exclusively through 5-HT2 receptors. There appear to be few, if any, 5-HT3 receptors in the VMN, and their functions are unclear. The inhibitory and the excitatory phases of the biphasic responses were not mediated together by a single receptor subtype but were mediated separately by 5-HT1A and 5-HT2 receptors, respectively. The presence of the biphasic response in a large proportion of neurons, therefore, indicates the coexistence of different subtypes of 5-HT receptors in many individual VMN neurons. The use of selective agonists and antagonists further indicates that the coexistence also occurs in neurons showing monophasic responses, and that the opposite actions mediated by the coexisting receptor subtypes can interact with each other. Therefore, changing the ratio of coexisting receptor subtypes could modify the net output of the VMN response to 5-HT. Together with behavioral studies by others, it emerges from our findings that the inhibitory action of 5-HT on VMN neurons is associated with, and may be responsible for, the stimulation of feeding and inhibition of lordosis, while the excitatory action is related and may lead to the opposite behavioral effects. Finally, with the coexistence in VMN neurons of two receptor subtypes that can mediate 5-HT effects on both feeding and lordosis, the VMN can serve as a substrate for 5-HT to coordinate these two behaviors.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Electrophysiology; Feeding Behavior; Female; In Vitro Techniques; Indoles; Neural Inhibition; Neurons; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Sexual Behavior, Animal; Tropisetron; Ventromedial Hypothalamic Nucleus