Serotonin-antagonist effects of 1-(1-naphthyl)piperazine on operant behavior of squirrel monkeys.
1-(1-Naphthyl)piperazine (1-NP) has been reported to have serotonin antagonist properties at the 5-HT2 subtype of receptor, and it has been suggested that it may have agonist actions at the 5-HT1 site. In the present experiments, the effects of 1-NP alone and in combination with a variety of 5-HT agonists, were studied in squirrel monkeys performing under a number of reinforcement schedules. The phenalkylamine hallucinogen 4-bromo-2,5-dimethoxyamphetamine (DOB, 0.01-0.3 mg/kg), which is thought to have predominant actions at 5-HT2 sites, reduced responding under fixed-interval (FI) schedules of presentation of food, and these decreases were blocked by 1-NP (0.3-1.0 mg/kg) or by the selective 5-HT2 antagonist, ketanserin (0.3 mg/kg). 1-(1-Naphthyl)piperazine also antagonized the decreases in responding produced by quipazine (0.1-5.6 mg/kg), another agonist with predominant 5-HT2 actions. 1-(m-Chlorophenyl)piperazine (mCPP, 0.1-3.0 mg/kg) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP, 0.1-3.0 mg/kg), both thought to act primarily at 5-HT1 sites, also decreased responding and this effect was blocked by methysergide and by 1-NP, but not by ketanserin. The effects of 1-NP (0.3-5.6 mg/kg) given alone were not like those of mCPP or TFMPP. 1-(1-Naphthyl)piperazine produced moderate increases in responding under shock-avoidance schedules, whereas only decreases in responding were seen after mCPP and TFMPP.(ABSTRACT TRUNCATED AT 250 WORDS)
Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545.
J W
JW
McKearney
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004597:Electroshock; D005260:Female; D005502:Food; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology; D012055:Reinforcement Schedule; D012453:Saimiri; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D012702:Serotonin Antagonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; C018406:1-(3-trifluoromethylphenyl)piperazine; C003943:2,5-dimethoxy-4-bromoamphetamine; D011814:Quipazine; C048241:1-(1-naphthyl)piperazine; C015068:1-(3-chlorophenyl)piperazine