Neural circuits underlying the inhibition of sympathetically‐mediated thermogenesis in brown adipose tissue (BAT) induced by atypical antipsychotic drugs

Abstract

Administration of atypical antipsychotic drugs suppresses sympathetic activation of metabolism in BAT, which may contribute to the weight gain observed with maintenance on these medications. This study investigated the neural circuitry responsible for the antipsychotic drug‐evoked inhibition of the sympathetic outflow to BAT. In urethane/chloralose anesthetized rats, the increase in BAT sympathetic nerve activity (SNA) evoked by cooling the core temperature to ~35.5°C was completely inhibited by the atypical antipsychotic drug, Clozapine (Cloz; 3mg/kg, iv). Bilateral microinjection of muscimol (2mM, 120nl/side) into the ventrolateral medulla (VLM) reversed or prevented the Cloz‐evoked inhibition of BAT SNA. In contrast to the effect of Cloz on the cooling response, the increase in BAT SNA evoked by blockade of GABAA receptors within the rostral raphe pallidus (RPa) was not inhibited by Cloz (3–6mg/kg, iv). These results suggest that neurons within the VLM play a role in the inhibition of BAT SNA evoked by atypical antipsychotic drugs, possibly by activating a GABAergic input to the RPa. Supported by NIH grant DK082558 and an American Heart Association SDG.