The σ ligand rimcazole activates noradrenergic neurons projecting to the paraventricular nucleus and increases corticosterone secretion in rats

Abstract

Intraperitoneal injection of rimcazole, a σ ligand, into male rats increased plasma concentrations of corticosterone in a dose- and time-related fashion. Concurrently, rimcazole increased concentrations of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus (PVN) of the hypothalamus, suggesting that the drug activates noradrenergic neurons terminating in this nucleus. This latter suggestion was confirmed by the finding that rimcazole also increased concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in the PVN. Pentazocine, a σ ligand was without effect per se, but blocked the ability of rimcazole to increase concentrations of MHPG in the PVN and corticosterone in plasma. Taken together, these results suggest that rimcazole activates noradrenergic neurons projecting to the PVN via a mechanism involving σ binding sites, and this action may be responsible for the ability of this drug to increase secretion of corticosterone.