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.
Filip
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Przegaliński
E
E
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004347:Drug Interactions; D008024:Ligands; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014230:Triazoles; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C088974:4-(3-(benzotriazol-1-yl)propyl)-1-(2-methoxyphenyl)piperazine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015068:1-(3-chlorophenyl)piperazine; D011224:Prazosin