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

• Published in: International journal of molecular sciences Vol. 22; no. 24; p. 13420
• Main Authors: Clauss, Nikki J, Koek, Wouter, Daws, Lynette C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.12.2021; MDPI
• Subjects: Addictions; amphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Biological Transport - drug effects; Cations; Cell Membrane - drug effects; Cell Membrane - metabolism; Central Nervous System Stimulants - pharmacology; conditioned place preference; Drug abuse; Drugs; Female; Females; Genotype & phenotype; Hypotheses; locomotion; Locomotion - drug effects; Male; Males; Membranes; Mice; Mice, Knockout; Monoamine transporter; Neurotransmission; Oct-4 protein; Octamer Transcription Factor-3 - metabolism; Organic cation transporter; organic cation transporter 3; Overdose; Place preference conditioning; plasma membrane monoamine transporter; Reward; Sensitizing; Stimulants; Vesicular Monoamine Transport Proteins - metabolism; amphetamine; plasma membrane monoamine transporter; conditioned place preference; organic cation transporter 3; locomotion
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413420

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.