Psychomotor stimulant effects of beta-phenylethylamine in monkeys treated with MAO-B inhibitors.
OBJECTIVE
Sufficiently high doses of beta-phenylethylamine (beta-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 beta-PEA in monkeys are modified by treatment with inhibitors of MAO-B [R-(-)-deprenyl and MDL 72974].


RESULTS
In studies of its S(D) effects, doses of beta-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 beta-PEA produced full substitution when administered after either R-(-)-deprenyl or MDL 72974 (0.3 mg/kg). The MA-like S(D) effects of beta-PEA were attenuated by either dopamine D(1) or D(2) receptor blockers. In studies of its S(R) effects, high doses of beta-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 beta-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 beta-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 beta-PEA in monkeys, presumably by delaying its inactivation. MAO-B inhibition leading to increased levels of beta-PEA may be useful, alone or in combination with other therapeutic agents, in the pharmacological management of selected aspects of drug dependence.
Bergman
J
J
Harvard Medical School, McLean Hospital/ADARC, 115 Mill Street, Belmont, MA 02478, USA. jbergman@hms.harvard.edu
Yasar
S
S
Winger
G
G
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012453:Saimiri; D012646:Self Administration / Q000379:methods
D000697:Central Nervous System Stimulants; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011619:Psychotropic Drugs; C029261:phenethylamine; D008995:Monoamine Oxidase