Differential increase in Fos immunoreactivity in hypothalamic and septal nuclei by arginine8-vasopressin and desglycinamide9-arginine8-vasopressin.

摘要

Subcutaneous or intracerebroventricular injection of either arginine8-vasopressin or desglycinamide9-arginine8-vasopressin has been shown to facilitate memory, reduce or reverse the effects of amnesic drugs, and maintain tolerance to some effects of ethanol. These actions of vasopressin (and, by inference, of desglycinamide9-arginine8-vasopressin) are mediated by vasopressin V1 receptors in brain, via a c-fos-dependent mechanism, but the receptors at which the desglycinamide analog acts have not been identified. The precise central sites are also not known, but evidence of several types suggested the anterior hypothalamus and septum as probable loci of vasopressin action. In the present work, this question was studied by immunocytochemistry, using antibodies against Fos and Fos-like proteins. The numbers of Fos-immunoreactive nuclei were counted in several related brain regions and structures, after administration of arginine8-vasopressin, des-Gly9-[Arg8]-vasopressin or saline. A subcutaneous injection of vasopressin, but not of saline, enhanced Fos expression in the paraventricular, supraoptic and suprachiasmatic nuclei of the hypothalamus, but the desglycinamide analog stimulated Fos expression only in the suprachiasmatic nucleus. Vasopressin injection significantly increased the number of Fos-immunoreactive cells in the intermediate lateral septum, medial septum, and dorsal and ventral divisions of the lateral septum. In contrast, the desglycinamide analog increased the numbers of Fos-immunoreactive cells in the dorsal and intermediate portions of the lateral septum, but caused no change in the medial septum, and a decrease in the ventral portion of the lateral septum. Increased Fos expression was also found in the subfornical organ after subcutaneous injection of either vasopressin or the desglycinamide analog. Double labeling with antibodies against Fos protein and against vasopressin revealed that most of the vasopressin-induced Fos-immunoreactive cells in the supraoptic, paraventricular and suprachiasmatic hypothalamic nuclei are also vasopressin immunoreactive, i.e. they are vasopressin-producing neurons. These findings suggest that a circuit involving V1 receptors in the subfornical organ, connecting fibres to the suprachiasmatic nucleus, and vasopressinergic projections from the suprachiasmatic nucleus to the lateral septum, may play a central role in mediating the actions of both vasopressin and its desglycinamide analog in the maintenance of ethanol tolerance.