GABA A/benzodiazepine receptor localization in the circadian timing system

Abstract

γ-Aminobutyric acid (GABA) and exogenous benzodiazepines are thought to play a role in the neural regulation of circadian rhythms. Because binding sites for the benzodiazepines and GABA A ligands are functionally coupled as part of the GABA A/benzodiazepine receptor complex (GABA A/BZR), we analyzed the localization of GABA neurons and GABA A/BZR within 3 nuclei involved in circadian rhythm regulation using autoradiographic and immunohistochemical techniques. Glutamic acid decar☐ylase-immunoreactive axons are present in the suprachiasmatic nuclei (SCN), intergeniculate leaflet (IGL), and dorsal raphe nucleus (DR). Immunoreactivity for the GABA A/BZ receptor complex is absent from the SCN and the IGL whereas the DR shows a dense, uniform immunoreactivity. Semiquantitative analysis of autoradiograms for [ 3H]diazepam and [ 3H]flunitrazepam binding reveals a moderate level of binding in the SCN, a low level of binding in the IGL, and the highest level of the DR. Based on both the pattern of benzodiazepine binding and of receptor immunoreactivity the DR would appear to be a likely target site for GABA A and benzodiazepine action. The SCN would also appear to be a possible target site. The results suggest the IGL is not a site for direct GABA A and benzodiazepine action, but do not exclude a role for the IGL in the neural circuitry mediating GABA and benzodiazepine interactions with the circadian system.