Psychomotor stimulant effects of beta-phenylethylamine in monkeys treated with MAO-B inhibitors

Abstract

Rationale and objective: Sufficiently high doses of β-phenylethylamine (β-PEA), a trace amine that is rapidly metabolized by monoamine oxidase-type B (MAO-B), can produce effects comparable to those of cocaine or methamphetamine (MA). The present experiments were conducted to study how the discriminative-stimulus (S D ) and reinforcing-stimulus (S R ) effects of β-PEA in monkeys are modified by treatment with inhibitors of MAO-B [R-(–)-deprenyl and MDL 72974]. Methods and results: In studies of its S D effects, doses of β-PEA up to 30 mg/kg engendered only sporadic responding on the drug-associated lever in squirrel monkeys that discriminated intramuscular injections of 0.3 mg/kg MA from vehicle whereas lower doses of 0.3–1.0 mg/kg β-PEA produced full substitution when administered after either R-(–)-deprenyl or MDL 72974 (0.3 mg/kg). The MA-like S D effects of β-PEA were attenuated by either dopamine D 1 or D 2 receptor blockers. In studies of its S R effects, high doses of β-PEA maintained responding in two of three monkeys under a second-order fixed-interval schedule (3.0 or 10 mg/kg per injection) and two of three monkeys under a simple fixed ratio (FR) schedule (0.3–1.0 mg/kg per injection) of intravenous (i.v.) self-administration. MAO-B inhibition by R-(–)-deprenyl or MDL 72974 enhanced the S R effects of β-PEA in all monkeys and, under the FR schedule, induced a 30-fold or greater leftward shift in the dose-response function for its i.v. self-administration. Based on time-course determinations, the enhanced S R effects of β-PEA under the FR schedule were long-lasting and dissipated gradually over 3–7 days. Conclusions: These results show that inhibition of MAO-B enhances S D and S R effects of β-PEA in monkeys, presumably by delaying its inactivation. MAO-B inhibition leading to increased levels of β-PEA may be useful, alone or in combination with other therapeutic agents, in the pharmacological management of selected aspects of drug dependence.