The 5-HT(1A) receptor antagonist p-MPPI blocks responses mediated by postsynaptic and presynaptic 5-HT(1A) receptors

The present experiments examined the ability of the novel 5-HT(1A) receptor antagonist to block responses mediated by postsynaptic and presynaptic 5-HT(1A) receptors in vivo. Pretreatment with p-MPPI reduced on blocked the effect of the 5-HT(1A) receptor agonist 8-OH-DPAT on two responses mediated by postsynaptic 5-HT(1A) receptors reduction of body temperature and the 5-HT behavioral syndrome. Administration of p-MPPI also clocked the ability of 8-OH-DPAT to reduce extracellular 5-HT in the striatum, a response mediated by presynaptic 5-HT(1A) 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-HT(1A) receptor antagonist in vivo with no intrinsic activity. p-MPPI may prove to be a useful pharmacological tool for studying 5-HT(1A) receptors and their involvement in anxiety and affective disorders.