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

J. Bergman; S. Yasar; G. Winger

doi:10.1007/s002130100890

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

J. Bergman, S. Yasar, G. Winger

School of Medicine

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23 Scopus citations

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 precent 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 D₁ or D₂ 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.

Original language	English (US)
Pages (from-to)	21-30
Number of pages	10
Journal	Psychopharmacology
Volume	159
Issue number	1
DOIs	https://doi.org/10.1007/s002130100890
State	Published - Dec 2001

Keywords

Drug abuse
Drug discrimination
Drug self-administration
MAO-B inhibition
Psychomotor stimulant
β-PEA

ASJC Scopus subject areas

Pharmacology

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10.1007/s002130100890

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@article{d9bd095ee65c4ecbb257e48f132c62c5,

title = "Psychomotor stimulant effects of β-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 precent experiments were conducted to study how the discriminative-stimulus (SD) and reinforcing-stimulus (SR) 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 SD 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 SD effects of β-PEA were attenuated by either dopamine D1 or D2 receptor blockers. In studies of its SR 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 SR 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 SR 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 SD and SR 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.",

keywords = "Drug abuse, Drug discrimination, Drug self-administration, MAO-B inhibition, Psychomotor stimulant, β-PEA",

author = "J. Bergman and S. Yasar and G. Winger",

note = "Funding Information: Acknowledgements The authors thank S.R. Goldberg and J.H. Woods for their careful reading of earlier versions of this manuscript and A.M. Pond, B. Winger, L. Heller, and D. Hutzinger for expert technical assistance. We also thank Chinoin Industries and Merrell-Dow Research Institute for generously donating drugs used in these experiments. This research was supported in part by USPHS grants DA03774, DA10566 (J.B.) and DA04403, DA05951, and DA00254 (G.W.). Facilities and services were provided in part by the New England Regional Primate Research Center (USPHS Division of Research Resources grant RR00168).",

year = "2001",

month = dec,

doi = "10.1007/s002130100890",

language = "English (US)",

volume = "159",

pages = "21--30",

journal = "Psychopharmacology",

issn = "0033-3158",

publisher = "Springer Verlag",

number = "1",

}

TY - JOUR

T1 - Psychomotor stimulant effects of β-phenylethylamine in monkeys treated with MAO-B inhibitors

AU - Bergman, J.

AU - Yasar, S.

AU - Winger, G.

N1 - Funding Information: Acknowledgements The authors thank S.R. Goldberg and J.H. Woods for their careful reading of earlier versions of this manuscript and A.M. Pond, B. Winger, L. Heller, and D. Hutzinger for expert technical assistance. We also thank Chinoin Industries and Merrell-Dow Research Institute for generously donating drugs used in these experiments. This research was supported in part by USPHS grants DA03774, DA10566 (J.B.) and DA04403, DA05951, and DA00254 (G.W.). Facilities and services were provided in part by the New England Regional Primate Research Center (USPHS Division of Research Resources grant RR00168).

PY - 2001/12

Y1 - 2001/12

N2 - 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 precent experiments were conducted to study how the discriminative-stimulus (SD) and reinforcing-stimulus (SR) 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 SD 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 SD effects of β-PEA were attenuated by either dopamine D1 or D2 receptor blockers. In studies of its SR 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 SR 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 SR 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 SD and SR 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.

AB - 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 precent experiments were conducted to study how the discriminative-stimulus (SD) and reinforcing-stimulus (SR) 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 SD 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 SD effects of β-PEA were attenuated by either dopamine D1 or D2 receptor blockers. In studies of its SR 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 SR 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 SR 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 SD and SR 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.

KW - Drug abuse

KW - Drug discrimination

KW - Drug self-administration

KW - MAO-B inhibition

KW - Psychomotor stimulant

KW - β-PEA

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DO - 10.1007/s002130100890

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JO - Psychopharmacology

JF - Psychopharmacology

IS - 1

ER -

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

Abstract

Keywords

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