Sites of action of thyrotropin-releasing hormone on central nervous system neurons revealed by expression of the immediate-early gene c-fos in the rat.

Centrally administered thyrotropin-releasing hormone produces a number of physiological and behavioral changes, e.g., a general antidepressant effect, increasing body temperature, and elevated blood pressure. However, the specific brain sites of action responsible for the centrally activating property of thyrotropin-releasing hormone have not been precisely determined. Using chloral hydrate-anesthetized adult Sprague-Dawley rats, we compared the distribution of Fos-like immunoreactivity after intracerebroventricular administration of thyrotropin-releasing hormone with the results after intracerebroventricular injection of vehicle alone. Some rats were paralysed and artificially ventilated to avoid possible Fos expression secondarily induced by autonomic (e.g., respiratory) disturbances. In thyrotropin-releasing hormone administered rats, selective Fos-like immunoreactivity was observed in V/VI layers of the pre- and infralimbic areas of the medial prefrontal cortex, the ventral midline thalamus, and the nucleus of the solitary tract as well as in the adjacent reticular formation. Fos-like immunoreactivity was significantly reduced in most areas of the cerebral cortex (II/III layers), the shell of the nucleus accumbens, the medial amygdaloid nucleus, parts of the hypothalamus, and the periaqueductal gray. These data suggest that various behavioral and autonomic responses induced by centrally administered thyrotropin-releasing hormone might be produced through the complex neural circuitry comprising the above structures, which are presumed to be implicated in limbic and/or autonomic functions.