Effects of MP-3022 on the 8-OH-DPAT-induced discriminative stimulus in rats

To examine the effects of 4-[3-(benzotriazol-1-yl)-propyl]-1-(2-methoxyphenyl)piperazine (MP-3022), a high affinity 5-HT1A ligand, on the 5-HT1A-induced stimulus effect and to compare its effects with those produced by some 5-HT1A receptor ligands, rats were trained to discriminate between 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 0.1 mg/kg ip, and saline in a standard, two-lever operant procedure. Substitution studies showed that the 8-OH-DPAT cue was mimicked in a dose-dependent manner by buspirone and ipsapirone, the 5-HT1A receptor partial agonists, but not by 1-(3-chlorophenyl)piperazine (m-CPP), a nonselective 5-HT agonist. Furthermore, the 8-OH-DPAT cue was almost completely blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)]butylpiperazine (NAN-190), a 5-HT1A receptor and alpha 1-adrenoceptor antagonist, but not by prazosin (a selective alpha 1-adrenoceptor blocker). Our results also demonstrate that the discriminative effect of 8-OH-DPAT may be dose-dependently antagonized by MP-3022, which itself does not mimic the cue. It is concluded that MP-3022 behaves like a full 5-HT1A receptor antagonist in the 8-OH-DPAT-evoked discrimination procedure.