DOWN-REGULATION OF 5-HT1A RECEPTORS IN RAT HYPOTHALAMUS AND DENTATE GYRUS AFTER BINGE PATTERN COCAINE ADMINISTRATION

The effect of chronic cocaine exposure on the central serotonergic sys tem in the rat was investigated using a selective 5-HT1A receptor agon ist, [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OHK-DPAT), and a 5 -HT2A receptor antagonist, [3H]ketanserin, as tritiated ligands in a q uantitative autoradiography study. Rats were administered cocaine in a ''binge'' pattern, 15 mg/kg/injection, three times a day, at 1-h inte rvals for 14 days to mimic the pattern often seen in human cocaine add icts. A significant decrease in the binding of [3H]8-OH-DPAT was found in the ventromedial hypothalamus (P < 0.001) and the dorsal dentate g yrus (P < 0.01) in rats administered cocaine as compared with rats inj ected with saline. No significant difference in the binding of [3H]ket anserin was found in frontal, parietal, agranular insular, and pirifor m cortices, caudate-putamen, olfactory tubercle, nucleus accumbens, th alamus, septohippocampal nucleus, and claustrum. Several studies have shown that 5-HT1A receptor agonists have antidepressant properties. Ot her studies, in animal models, have shown that 5-HT1A receptor agonist s stimulate the hypothalamic-pituitary-adrenal axis, which is of inter est, since chronic activation of this axis has been related to anxiety and depression. Our data show that the 5-HT1A component of the seroto nergic system is altered following chronic ''binge'' pattern cocaine a dministration in an animal model and may be related to changes in the HPA axis and behavior. Synapse 30:166-171, 1998. (C) 1998 Wiley-Liss, Inc.