Alpha1 receptor antagonist in the median raphe nucleus evoked hyperphagia in free-feeding rats

Serotonergic neurons in the median raphe nucleus (MnR) are stimulated by α1-adrenergic agonists and inhibited by α2-agonists. This study investigated the effect of the blockade of the MnR α1-adrenergic receptors of free feeding rats as an attempt to elucidate the functional role of these receptors in the control of feeding behavior. In addition, an α2-receptor antagonist was also administered in the MnR in order to strengthen the previous suggestion that α2-adrenergic receptors participate in the control of feeding behavior, probably decreasing the facilitatory influence on MnR serotonergic neurons. The α1-adrenergic antagonist prazosin (PRA, 40 nmol) or vehicle was injected into the MnR 15 min before treatment with phenylephrine (PHE, 0.2 nmol). The α2-adrenergic antagonist yohimbine (YOH, 40 nmol) was administered 15 min before clonidine (CLO, 20 nmol) or vehicle in free-feeding rats. After the injections, the animals were placed in the feeding chamber for 30 min to evaluate the ingestive and non-ingestive behaviors. At the end of the experiment the quantity of food and water consumed were measured. While treatment with PRA in the MnR followed by PHE did not change the feeding behavior, PRA injection alone into the MnR caused hyperphagia accompanied by a reduction in the latency to start eating, an increase in feeding frequency and an increase in the feeding duration. Pretreatment with YOH in the MnR blocked the hyperphagic effect induced by CLO. The present data reinforce our previous suggestion that the MnR α2-adrenergic receptors participate in the control of feeding behavior, probably decreasing the facilitatory influence on MnR serotonergic neurons of free-feeding animals. Furthermore, these results indicate that this influence is tonically mediated by α1-adrenergic receptors upon MnR neurons, which inhibit food intake.