Role of Organic Cation Transporter 3 and Plasma Membrane Monoamine Transporter in the Rewarding Properties and Locomotor Sensitizing Effects of Amphetamine in Male AndFemale Mice

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Dec 24

PMID 34948221

Citations 11

Authors

Nikki J Clauss

Wouter Koek

Lynette C Daws

Affiliations

Soon will be listed here.

Abstract

A lack of effective treatment and sex-based disparities in psychostimulant addiction and overdose warrant further investigation into mechanisms underlying the abuse-related effects of amphetamine-like stimulants. Uptake-2 transporters such as organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT), lesser studied potential targets for the actions of stimulant drugs, are known to play a role in monoaminergic neurotransmission. Our goal was to examine the roles of OCT3 and PMAT in mediating amphetamine (1 mg/kg)-induced conditioned place preference (CPP) and sensitization to its locomotor stimulant effects, in males and females, using pharmacological, decynium-22 (D22; 0.1 mg/kg, a blocker of OCT3 and PMAT) and genetic (constitutive OCT3 and PMAT knockout (-/-) mice) approaches. Our results show that OCT3 is necessary for the development of CPP to amphetamine in males, whereas in females, PMAT is necessary for the ability of D22 to prevent the development of CPP to amphetamine. Both OCT3 and PMAT appear to be important for development of sensitization to the locomotor stimulant effect of amphetamine in females, and PMAT in males. Taken together, these findings support an important, sex-dependent role of OCT3 and PMAT in the rewarding and locomotor stimulant effects of amphetamine.

Citing Articles

Organic cation transporters in psychiatric and substance use disorders.

Honan L, Fraser-Spears R, Daws L Pharmacol Ther. 2023; 253:108574.

PMID: 38072333 PMC: 11052553. DOI: 10.1016/j.pharmthera.2023.108574.

Heterotypic Stressors Unmask Behavioral Influences of PMAT Deficiency in Mice.

Weber B, Nicodemus M, Hite A, Spalding I, Beaver J, Scrimshaw L Int J Mol Sci. 2023; 24(22).

PMID: 38003684 PMC: 10671398. DOI: 10.3390/ijms242216494.

Heterotypic stressors unmask behavioral influences of PMAT deficiency in mice.

Weber B, Nicodemus M, Hite A, Spalding I, Beaver J, Scrimshaw L bioRxiv. 2023; .

PMID: 37693400 PMC: 10491137. DOI: 10.1101/2023.08.30.555632.

Are There Prevalent Sex Differences in Psychostimulant Use Disorder? A Focus on the Potential Therapeutic Efficacy of Atypical Dopamine Uptake Inhibitors.

Hersey M, Bartole M, Jones C, Newman A, Tanda G Molecules. 2023; 28(13).

PMID: 37446929 PMC: 10343811. DOI: 10.3390/molecules28135270.

Ethanol inhibits dopamine uptake via organic cation transporter 3: Implications for ethanol and cocaine co-abuse.

Clauss N, Mayer F, Owens W, Vitela M, Clarke K, Bowman M Mol Psychiatry. 2023; 28(7):2934-2945.

PMID: 37308680 PMC: 10615754. DOI: 10.1038/s41380-023-02064-5.

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