Drug-Induced Regulation of [¹²⁵I]Iodocyanopindolol-labeled 5-Hydroxytryptamine_1B Receptor Binding Sites in the Central Nervous System

Abstract

Little is known about the regulation of 5-hydroxytryptaminew (5-HT_1B) receptors, a putative terminal autoreceptor in the central nervous system. We studied the regional responses of [¹²⁵I]iodocyanopindolol ([¹²⁵I]ICYP)-labeled central 5-HT_1B sites to chronic treatment with 5-HT agonists and antagonists at a dose of 10 mg/kg/d IP for 30 consecutive days in the rat. In controls, there were 3.4-fold regional differences in B_max, with a rank order of brainstem > hippocampus > cortex, striatum > spinal cord, and K_aS were slightly lower in striatum and spinal cord. RU 24969 significantly reduced B_max 23 to 63% in cortex, hippocampus, striatum, brainstem, and spinal cord without a change in K_a except for a 1.7-fold increase in cortex and spinal cord. The putative 5-HT_1B agonist (m-trifluoromethyl-phenylpiperazine (TFMPP), but not [l-(3-chlorophenyl)piperazine] (m-CPP) or the 5-HT_1B antagonists pindolol or quipazine, reduced the B_max of cortical 5-HT_1B sites (−16%). Chronic treatment with the 5-HT antagonists methysergide, pindolol, propranolol, ritanserin, metergoline, or methiothepin did not significantly affect striatal B_max or K_d compared to respective vehicles. The data demonstrate significant changes in maximum number of 5-HT_1B receptors in response to chronic agonist but not antagonist treatments at the dose studied.

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