Analyzing sex differences in how reduced function of plasma membrane monoamine transporters (PMAT) in mice affects learning to work for positive reinforcers

Abstract ID 94463 Poster Board 122 Plasma membrane monoamine transporter (PMAT, Slc29a4) is a low affinity, high capacity monoamine neurotransmitter transporter of dopamine and serotonin. Around 30% of humans have a PMAT polymorphism associated with reduced PMAT function. How reduced PMAT function affects behavior remains largely unknown, particularly because there are no drugs that selectively inhibit PMAT. Thus, the objective of this study was to use genetically modified PMAT-deficient mice in an appetitive operant conditioning study to investigate how reduced PMAT function impacts performance of behaviors required to obtain a desirable outcome (food reinforcer). In this study, we used mice of both sexes across all three genotypes (+/+, +/−, −/−). During appetitive operant, the mice were sequentially trained on fixed ratio (FR)-1, -3, and -5 schedules, followed by a progressive ratio (PR) schedule. After attaining PR stability, mice underwent an 8 wk hold during which no behavior occurred. Then, they experienced a brief swim stress to explore how PMAT deficiency affects subsequent PR performance. We hypothesized PMAT knockout mice would perform better in operant behavior, completing FR schedules before their wildtype and heterozygous counterparts due to absence of PMAT function prolonging serotonergic and/or dopaminergic signaling. Thus far, we've observed that all female and male KO mice completed FR & PR schedules within their first 40 days, as opposed to their respective sex WT counterparts still actively running after 95+ days. Because male mice are still being run, and not all female mice have completed swim stress, we cannot yet make definitive conclusions about the interactions of genes × environment × sex. Nevertheless, these findings so far suggest that normal PMAT function impedes acquisition of behavioral procedures that result in appetitive outcomes in mice. Given we have found sex-specific effects of PMAT in other dimensions of behavior, we expect to observe significant sex differences in terms of these operant behaviors too. Future directions for this project include evaluating the necessity of sex hormones in these PMAT-deficient shifts, as well as further characterization of how stress interacts with sex and genotype to alter operant performance. Funding: This work was supported by a Brain Health Research Institute (BHRI) Gold Award and University Research Council Supplement from Kent State University to TLG. LRS was supported by these funds, as well as by Kent State University's Summer Undergraduate Research Experience Program and the BHRI Summer Fellows Program.