Serotonin-antagonist effects of 1-(1-naphthyl)piperazine on operant behavior of squirrel monkeys

Abstract

1-(1-Naphthyl)piperazine (1-NP) has been reported to have serotonin antagonist properties at the 5-HT 2 subtype of receptor, and it has been suggested that it may have agonist actions at the 5-HT 1 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-HT 2 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-HT 2 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-HT 2 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-HT 1 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. All three drugs produced similar decreases in responding under food schedules, but the effects of mCPP and TFMPP were blocked by the non-selective 5-HT antagonist, methysergide (0.3 mg/kg) and not by the 5-HT 2 antagonist, ketanserin whereas the effects of 1-NP were not changed by either of these antagonists. Thus, it would appear that 1-NP is an effective and non-selective 5-HT antagonist under these conditions and that its 5-HT agonist properties, if any, differ from those of mCPP and TFMPP.