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 recep tor antagonist to block responses mediated by postsynaptic and presyna ptic 5-HT1A receptors in vivo. Pretreatment with p-MPPI reduced or blo cked the effect of the 5-HT1A receptor agonist 8-OH-DPAT on two respon ses mediated by postsynaptic 5-HT1A receptors, reduction of body tempe rature and the 5-HT behavioral syndrome. Administration of p-MPPI alon e did not after body temperature or produce symptoms of the 5-HT syndr ome. Pretreatment with p-MPPI also blocked the ability of 8-OH-DPAT to reduce extracellular 5-HT in the striatum, a response mediated by pre synaptic 5-HT1A receptors in the dorsal raphe nucleus, but did not alt er striatal 5-HT when administered alone. These results indicate that p-MPPI is an effective 5-HT1A receptor antagonist in vivo with no intr insic activity. p-MPPI may prove to be a useful pharmacological tool f or studying 5-HT1A receptors and their involvement in anxiety and affe ctive disorders. (C) 1997 Elsevier Science Inc.