Drug-induced regulation of [125I]iodocyanopindolol-labeled 5-hydroxytryptamine1B receptor binding sites in the central nervous system.
Little is known about the regulation of 5-hydroxytryptamine1B (5-HT1B) receptors, a putative terminal autoreceptor in the central nervous system. We studied the regional responses of [125I]iodocyanopindolol ([125I]ICYP)-labeled central 5-HT1B 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 Bmax, with a rank order of brainstem > hippocampus > cortex, striatum > spinal cord, and Kas were slightly lower in striatum and spinal cord. RU 24969 significantly reduced Bmax 23 to 63% in cortex, hippocampus, striatum, brainstem, and spinal cord without a change in Ka except for a 1.7-fold increase in cortex and spinal cord. The putative 5-HT1B agonist (m-trifluoromethyl-phenylpiperazine (TFMPP), but not [1-(3-chlorophenyl)piperazine] (m-CPP) or the 5-HT1B antagonists pindolol or quipazine, reduced the Bmax of cortical 5-HT1B sites (-16%). Chronic treatment with the 5-HT antagonists methysergide, pindolol, propranolol, ritanserin, metergoline, or methiothepin did not significantly affect striatal Bmax or Kd compared to respective vehicles. The data demonstrate significant changes in maximum number of 5-HT1B receptors in response to chronic agonist but not antagonist treatments at the dose studied.
Pranzatelli
M R
MR
Department of Neurology, George Washington University, Washington, DC.
Razi
P
P
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D020120:Iodocyanopindolol; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D020120:Iodocyanopindolol; D010869:Pindolol