The 5-HT1A receptor antagonist p-MPPI blocks responses mediated by postsynaptic and presynaptic 5-HT1A receptors.
The present experiments examined the ability of the novel 5-HT1A receptor antagonist to block responses mediated by postsynaptic and presynaptic 5-HT1A receptors in vivo. Pretreatment with p-MPPI reduced or blocked the effect of the 5-HT1A receptor agonist 8-OH-DPAT on two responses mediated by postsynaptic 5-HT1A receptors, reduction of body temperature and the 5-HT behavioral syndrome. Administration of p-MPPI alone did not alter body temperature or produce symptoms of the 5-HT syndrome. Pretreatment with p-MPPI also blocked the ability of 8-OH-DPAT to reduce extracellular 5-HT in the striatum, a response mediated by presynaptic 5-HT1A receptors in the dorsal raphe nucleus, but did not alter striatal 5-HT when administered alone. These results indicate that p-MPPI is an effective 5-HT1A receptor antagonist in vivo with no intrinsic activity. p-MPPI may prove to be a useful pharmacological tool for studying 5-HT1A receptors and their involvement in anxiety and affective disorders.
Allen
A R
AR
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104-2649, USA.
Singh
A
A
Zhuang
Z P
ZP
Kung
M P
MP
Kung
H F
HF
Lucki
I
I
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000631:Aminopyridines; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin