Injections of the of the α1-adrenoceptor antagonist prazosin into the median raphe nucleus increase food intake and Fos expression in orexin neurons of free-feeding rats

Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response. For this purpose, we examined the induction of c-Fos immunoreactivity in forebrain structures following injections of the α1-adrenoceptor antagonist prazosin into the MnR of free-feeding rats. To determine the chemical identity of hypothalamic c-Fos-positive cells, we then conducted double-label immunohistochemistry for Fos/orexin (OX) or Fos/melanin-concentrating hormone (MCH). Finally, we combined anterograde tracing from the MnR with immunohistochemical detection of orexin. Prazosin injections into the MnR significantly increased food intake. The ingestive response was accompanied by an increase in Fos expression in the basolateral amygdala (BLA) and lateral hypothalamic area (LHA). In the LHA, Fos expression occurred in neurons expressing OX, but not MCH. Combined anterograde tracing experiments revealed that LHA OX neurons are prominently targeted by MnR axons. These findings suggest that intra-MnR injection of prazosin, via activation of orexinergic neurons in the LHA and non-orexinergic neurons in the BLA, evoked a motivational response toward food intake.