Injections of the α-2 adrenoceptor agonist clonidine into the dorsal raphe nucleus increases food intake in satiated rats

The present study aimed to evaluate the effects of pharmacological manipulation of alpha-adrenergic agonists in the dorsal raphe nucleus (DR) on food intake in satiated rats. Adult male Wistar rats with chronically implanted cannula in the DR were injected with adrenaline (AD) or noradrenaline (NA) (both at doses of 6, 20 and 60 nmol), or alpha-1 adrenergic agonist phenylephrine (PHE) or alpha-2 adrenergic agonist clonidine (CLO) (both at doses of 6 and 20 nmol). The injections were followed by the evaluation of ingestive behaviors. Food and water intake were evaluated for 60 min. Administration of AD and NA at 60 nmol and CLO at 20 nmol increased food intake and decreased latency to start consumption in satiated rats. The ingestive behavior was not significantly affected by PHE treatment in the DR. CLO treatment increased Fos expression in the arcuate nucleus (ARC) and paraventricular nucleus of the hypothalamus (PVN) in rats that were allowed to eat during the experimental recording (AF group). However, when food was not offered during the experiment (WAF group), PVN neurons were not activated, whereas, neuronal activity remained high in the ARC when compared to control group. Noteworthy, ARC POMC neurons expressed Fos in the AF group. However, double-labeled POMC/Fos cells were absent in the ARC of the WAF group, although an increase in Fos expression was observed in non-POMC cells after CLO injections in the WAF group. In conclusion, the data from the present study highlight that the pharmacological activation of DR alpha-adrenoceptors affects food intake in satiated rats. The feeding response evoked by CLO injections into DR was similar to that induced by NA or AD injections, suggesting that the hyperphagia after NA or AD treatment depends on alpha-2 adrenoceptors activation. Finally, we have demonstrated that CLO injections into DR impact neuronal activity in the ARC, possibly evoking a homeostatic response toward food intake.