The Effect of Cocaine Conditioning on Lateral Preoptic Area Glutamatergic and GABAergic Activity

The lateral preoptic area (LPO) is a brain region that is involved in a wide range of homeostatic and motivational processes, such as reward processing and by extension, various aspects of substance use. While it is clear that the positioning of the LPO, as a result of its projections to and from other notable regions related to reward such as the ventral tegmental area (VTA) and the lateral habenula (LHb), associate the brain region with reward processing centers, the activity LPO's own neurons and how they relate to cocaine use have not been fully explicated. To examine the effects of cocaine on the LPO's local neuron population activity, we studied LPO glutamate and GABA neuron populations in VGat::cre and VGlut2::cre mice placed in cocaine conditioned place preference paradigms. In this paradigm, distinct locations of the apparatus were paired with either cocaine or saline administration. The activity of both glutamate and GABA neuron populations were recorded by fiber photometry before and after the behavioral paradigm. The neural recordings that occurred in the saline paired location were compared to the recordings from the cocaine paired locations. The activity of the two mice genotypes were also compared, allowing us to study the neural activity of both GABA and glutamate neurons at the LPO before and after the behavioral paradigms. Our results indicate the behavioral conditioning paradigm was sufficient in driving a preference to the cocaine-paired chamber. GABAergic activity, measured by the area under the curve (AUC) of the fiber photometry trace of VGat::Cre mice, correlated with a greater time spent on the cocaine paired chamber when compared to the pretest. The glutamatergic activity of VGlut2::Cre mice did not significantly change as a result of the pairing paradigm.

Pavankumar Yecham