Glutamate is the major excitatory neurotransmitter in the hypothalamus, which exerts its effects by activating ion channel-forming (ionotropic) or G-protein-coupled (metabotropic) receptors. Kainate-preferring glutamate receptor subunits (GluR5, GluR6, GluR7, KA1, and KA2) form one of the three ionotropic receptor families. In the present study, we analyzed the distribution of GluR5 subunit protein in the rat hypothalamus with immunohistochemistry. GluR5 immunoreactivity was observed in perikarya and processes of many hypothalamic cells some of which, based upon their morphological differentiation by size and structure, appeared to be neurons and others glial cells. Analyses revealed that higher number of glial cells were GluR5 positive when compared to the moderate number of GluR5-labeled neurons in the anteroventral periventricular nucleus. Numerous GluR5-expressing neurons and similar number of glia were detected in the suprachiasmatic nucleus. In the arcuate nucleus more glial cells were identified with GluR5 immunoreactivity than the number of labeled neurons. Scattered GluR5-positive cells were present in the periventricular nucleus. Specific immunostaining was not seen in the ventromedial nucleus or dorsomedial nucleus. In conclusion, it is suggested that the GluR5 subunits participate in the glutamatergic regulation of several neuroendocrine systems, such as the tubero-infundibular systems as well as in the control of circadian output through neuron-to-neuron and/or neuron-to-glia interactions. (c) 2005 Elsevier B.V All rights reserved.