RT Journal Article SR Electronic T1 Effects of Withdrawal from Cocaine Self-Administration on Rat Orbitofrontal Cortex Parvalbumin Neurons Expressing Cre recombinase: Sex-Dependent Changes in Neuronal Function and Unaltered Serotonin Signaling JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0017-21.2021 DO 10.1523/ENEURO.0017-21.2021 VO 8 IS 4 A1 Andrew M. Wright A1 Agustin Zapata A1 Alexander F. Hoffman A1 Julie C. Necarsulmer A1 Lamarque M. Coke A1 Reinis Svarcbahs A1 Christopher T. Richie A1 James Pickel A1 Bruce T. Hope A1 Brandon K. Harvey A1 Carl R. Lupica YR 2021 UL http://www.eneuro.org/content/8/4/ENEURO.0017-21.2021.abstract AB The orbitofrontal cortex (OFC) is a brain region involved in higher-order decision-making. Rodent studies show that cocaine self-administration (CSA) reduces OFC contribution to goal-directed behavior and behavioral strategies to avoid drug intake. This change in OFC function persists for many weeks after cocaine withdrawal, suggesting involvement in the process of addiction. The mechanisms underlying impaired OFC function by cocaine are not well-understood. However, studies implicate altered OFC serotonin (5-HT) function in disrupted cognitive processes during addiction and other psychiatric disorders. Thus, it is hypothesized that cocaine impairment of OFC function involves changes in 5-HT signaling, and previous work shows that 5-HT1A and 5-HT2A receptor-mediated effects on OFC pyramidal neurons (PyNs) are impaired weeks after cocaine withdrawal. However, 5-HT effects on other contributors to OFC circuit function have not been fully investigated, including the parvalbumin-containing, fast-spiking interneurons (OFCPV), whose function is essential to normal OFC-mediated behavior. Here, 5-HT function in naive rats and those withdrawn from CSA were evaluated using a novel rat transgenic line in which the rat parvalbumin promoter drives Cre-recombinase expression to permit identification of OFCPV cells by fluorescent reporter protein expression. We find that whereas CSA altered basal synaptic and membrane properties of the OFCPV neurons in a sex-dependent manner, the effects of 5-HT on these cells were unchanged by CSA. These data suggest that the behavioral effects of dysregulated OFC 5-HT function caused by cocaine experience are primarily mediated by changes in 5-HT signaling at PyNs, and not at OFCPV neurons.