This experiment tested the effect of clozapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures were monitored in urethane-anesthetized male Sprague-Dawley rats before and for 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same procedure was carried out in rats treated with orexin A plus an intraperitoneal administration of clozapine (8 mg/kg bw), an atypical antipsychotic that is largely used in the therapy of schizophrenia. The same variables were monitored in rats with clozapine alone. A group of rats with saline injection served as control. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures. Clozapine blocks completely the reactions due to orexin A. These findings suggest that clozapine influences strongly the thermogenic role of orexin A. Furthermore, the remarkable hyperthermic role played by orexin A is confirmed.
This experiment tested the effect of risperidone on the sympathetic and thermogenic effects induced by orexin A. The firing rates of sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colon temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 2 hours after the injection. The same variables were monitored in rats with an intraperitoneal administration of risperidone (50 mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is enhanced by the injection of risperidone. These findings suggest that risperidone elevates the responses due to orexin,
probably through an involvement of serotoninergic and dopaminergic pathways, which are affected by risperidone. Furthermore, we suggested the name "hyperthermine A" as additional denomination of "orexin A" by considering the strong influence of this neuropeptide on body temperature.