1The University of Texas at Dallas, School of Behavioral and Brain Sciences, Richardson TX, USA
Projects in my laboratory examine neuroadaptations in the medial prefrontal cortex (mPFC) which contribute to a loss of response inhibition in the PFC during the development and maintenance of alcohol addiction. To this end we use chronic intermittent ethanol vapor exposure (CIE), combined with a limited access paradigm, or operant conditioning for alcohol rewards, respectively, as two mouse models of alcohol drinking. We then study changes in behavior (e.g. attentional set-shifting and novel object recognition), as well as changes in synaptic transmission in the mPFC that result from alcohol exposure under these different conditions. We have previously shown that CIE leads to an increase in the ratio of NMDA to AMPA currents in mPFC pyramidal cells, and a similar shift can also be seen following alcohol self-administration in our operant paradigm. These changes at the NMDA receptor alter integrative properties in mPFC pyramidal neurons and they affect synaptic plasticity, which may disrupt PFC-dependent behaviors. Consistent with this idea, both CIE and goal-directed alcohol consumption in the operant paradigm operant impair cognitive flexibility in an attentional set-shifting task and this effect can be reversed by acamprosate. Here, I will present data from our ongoing work that examines acamprosate’s effects on glutamatergic transmission and NMDA receptor function in animals from our 2 behavioral paradigms.