PT  - JOURNAL ARTICLE
AU  - Jose Ignacio Pena-Bravo
AU  - Rachel Penrod
AU  - Carmela M. Reichel
AU  - Antonieta Lavin
TI  - Methamphetamine Self-Administration Elicits Sex-Related Changes in Postsynaptic Glutamate Transmission in the Prefrontal Cortex
AID  - 10.1523/ENEURO.0401-18.2018
DP  - 2019 Jan 01
TA  - eneuro
PG  - ENEURO.0401-18.2018
VI  - 6
IP  - 1
4099  - http://www.eneuro.org/content/6/1/ENEURO.0401-18.2018.short
4100  - http://www.eneuro.org/content/6/1/ENEURO.0401-18.2018.full
SO  - eNeuro2019 Jan 01; 6
AB  - Preclinical 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 (PL-PFC) of male and female 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 SA; 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 NMDA receptors (NMDAR) in the PFC of female rats. Our results may provide a mechanistic explanation for the sex differences reported for METH addiction in females.