Thyrotropin-releasing hormone: central site of action in antagonism of pentobarbital narcosis

Abstract

THYROTROPIN-RELEASING HORMONE (TRH) is capable of antagonising pentobarbital narcosis, and this effect is independent of its hypophysiotropic function^1,2. The potency of intraventricular injections^2,3 and the localisation of TRH in nerve terminals from both hypothalamic and extrahypothalamic sites^4,5, suggest that TRH may function as a neuromodulator in the central nervous system (CNS)⁶. Although TRH antagonism of pentobarbital has been behaviourally and electroencephalographically^7,8 characterised, the underlying neuroanatomical substrate remains unknown. In an attempt to identify the central substrate mediating this effect, we have used intracerebral microinjection of TRH into specific brain loci. Brain sites were chosen to represent large neuroanatomical regions—as cholinergic activation has been hypothesised to mediate pentobarbital antagonism by TRH, structures belonging to the cholinergic activating system⁹ were examined, and we also examined medially located brain regions that Wei et al.¹⁰ found to be most active at inducing TRH-mediated shaking. While a number of sites were found responsive at 500 ng of TRH, the septal region proved exceptionally sensitive by responding significantly at only 5.0 ng TRH.