RT Journal Article SR Electronic T1 Abstinence from cocaine-induced conditioned place preference produces discrete changes in glutamatergic synapses onto deep layer 5/6 neurons from prelimbic and infralimbic cortices JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0308-17.2017 DO 10.1523/ENEURO.0308-17.2017 A1 José I. Pena-Bravo A1 Carmela M. Reichel A1 Antonieta Lavin YR 2017 UL http://www.eneuro.org/content/early/2017/12/04/ENEURO.0308-17.2017.abstract AB Glutamatergic signaling in the medial prefrontal cortex (mPFC) plays a critical role in drug addiction and relapse. The mPFC is functionally subdivided into dorsal (prelimbic; PL) and ventral (infralimbic; IL) regions, and evidence suggests a differential role of these two divisions in the control of drug seeking and taking; however, there is a dearth of information on the cocaine-induced adaptations in PL- and IL-mPFC synaptic glutamate transmission and their regulation of behavioral responses to cocaine-associated stimuli. We tested male rats in a cocaine-induced conditioned place preference (CPP) paradigm. In vitro whole cell recordings were performed at different abstinence intervals to investigate the neuroadaptations in synaptic glutamate transmission in PL- and IL-mPFC deep layer (5/6) pyramidal neurons. Our results show that in naïve animals, PL-mPFC neurons expressed higher frequency of spontaneous events (sEPSCs), than IL-mPFC neurons. Following cocaine-CPP and a short abstinence period (8 days), we observed decreases in the amplitude of sEPSCs in both mPFC regions. Longer abstinence periods (30 days), resulted in a sustained decrease in the frequency of sEPSCs and an increase in AMPA receptor rectification only in PL-mPFC neurons. In addition, PL-mPFC neurons expressed a decrease in the area under the curve of sEPSCs, suggesting altered receptor activation dynamics. Synaptic glutamate transmission was not significantly different between re-tested and naïve rats. These results suggest that retention of cocaine-CPP requires differential modulation of glutamate transmission between PL- and IL-mPFC neurons and that these adaptations are dependent on the abstinence interval and re-exposure to the cocaine context.Significance Statement Addicted individuals have cognitive impairments associated with abnormal PFC function. Preclinical studies suggest that PL- and IL- mPFC glutamatergic output neurons play opposing roles in the control of addiction-related behaviors. Therefore, we used PFC slice recordings from male rats after abstinence from cocaine-CPP to measure the cocaine-evoked changes in glutamate transmission. We show for the first time that in naïve rats, PL-mPFC neurons exhibit a higher frequency of spontaneous excitatory currents compared to IL-mPFC neurons. In addition, synaptic glutamate transmission is selectively altered in rats that are not exposed to the conditioning context; and prolonged abstinence from cocaine-CPP produces an overall increase in the kinetics of spontaneous excitatory currents. Reversing these glutamate changes might prevent retention of cocaine-context associations.