TY - JOUR T1 - Methamphetamine self-administration elicits sex related changes in postsynaptic glutamate transmission in the prefrontal cortex JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0401-18.2018 SP - ENEURO.0401-18.2018 AU - Jose Ignacio Pena-Bravo AU - Rachel Penrod AU - Carmela M Reichel AU - Antonieta Lavin Y1 - 2019/01/10 UR - http://www.eneuro.org/content/early/2019/01/10/ENEURO.0401-18.2018.abstract N2 - Pre-clinical and clinical research has shown that females are more vulnerable to the rewarding effects of stimulants, and it has been proposed that estrogens may play a role in this enhanced sensitivity; however sex differences in methamphetamine (METH)-induced neuroplasticity have not been explored. To address this gap in knowledge we recorded from the prelimbic area of the prefrontal cortex (PFC) of male and females rats following long access METH self-administration (SA) and investigated the resulting long-term synaptic neuroadaptations. Males and females took similar amounts of METH during self-administration; however, female rats exhibit significant synaptic baseline differences when compared to males. Furthermore, females exhibited a significant increase in evoked excitatory currents. This increase in evoked glutamate was correlated with increases in NMDA currents and was not affected by application of a GluN2B selective blocker. We propose that METH SA selectively upregulates GluN2B-lacking NMDAR in the PFC of female rats. Our results may provide a mechanistic explanation for the sex differences reported for METH addiction in females.Significance Statement The rate of methamphetamine (METH) addiction is second only to heroin, and use trends are on the rise. Like other drugs of abuse, there are known sex differences in METH addiction, however if these differences result from sex differences in pharmacokinetics, neurophysiology, and/or drug-induced neuroplasticity has not been established. Here we assessed METH self-administration induced neuroadaptations in synaptic physiology using electrophysiological measures in prefrontal cortical brain slices of male and female rats. We are the first to report, to our knowledge, that cortical baseline and METH-induced synaptic responses are different between male and female rats. Our results may provide a mechanistic explanation for the sex differences reported for METH addiction in females and highlight the possibility that sex-specific treatment strategies may be required to address METH-induced neuroplasticity. ER -