Downregulation of 5-HT1A receptors in rat hypothalamus and dentate gyrus after “binge” pattern cocaine administration
✍ Scribed by Guillaume Perret; James H. Schluger; Ellen M. Unterwald; Jason Kreuter; Ann Ho; Mary Jeanne Kreek
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 274 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
The effect of chronic cocaine exposure on the central serotonergic system in the rat was investigated using a selective 5-HT1A receptor agonist, [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), and a 5-HT2A receptor antagonist, [3H]ketanserin, as tritiated ligands in a quantitative autoradiography study. Rats were administered cocaine in a ''binge'' pattern, 15 mg/kg/injection, three times a day, at 1-h intervals for 14 days to mimic the pattern often seen in human cocaine addicts. A significant decrease in the binding of [3H]8-OH-DPAT was found in the ventromedial hypothalamus (P Ͻ 0.001) and the dorsal dentate gyrus (P Ͻ 0.01) in rats administered cocaine as compared with rats injected with saline. No significant difference in the binding of [3H]ketanserin was found in frontal, parietal, agranular insular, and piriform cortices, caudate-putamen, olfactory tubercle, nucleus accumbens, thalamus, septohippocampal nucleus, and claustrum. Several studies have shown that 5-HT1A receptor agonists have antidepressant properties. Other studies, in animal models, have shown that 5-HT1A receptor agonists stimulate the hypothalamic-pituitary-adrenal axis, which is of interest, since chronic activation of this axis has been related to anxiety and depression. Our data show that the 5-HT1A component of the serotonergic system is altered following chronic ''binge'' pattern cocaine administration in an animal model and may be related to changes in the HPA axis and behavior.