Metabotropic glutamate receptor function in cocaine

University Of California San Francisco, San Francisco CA

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Abstract

DESCRIPTION: (provided by the applicant) The ventral tegmental area (VTA) is a brain region that is crucial for the expression of the rewarding effects of many addictive drugs. Recently, a novel metabotropic glutamate receptor (mGluR) inhibitory post-synaptic potential (IPSP) was reported in VTA dopaminergic neurons. Psychostimulants such as amphetamine inhibit this mGluR-mediated IPSP, thereby increasing the firing rate of dopaminergic neurons in this region. The proposed studies will enable us to determine if this IPSP differs between animals that are vulnerable to cocaine self-administration and those that are not. Animals will be behaviorally assayed by using a locomotor activity box and cocaine self-administration paradigm prior to VTA slice electrophysiology. We hypothesize that vulnerable animals have a desensitized MGluR response and therefore have less basal inhibition of VTA dopaminergic neurons, resulting in a larger efflux of dopamine into VTA target regions. Differences in the desensitization of the mGluR in this brain region could prove to be a molecular predictor of propensity to administer drugs of abuse. The data from these studies will potentially aid in our understanding of individual differences in vulnerability to drug-seeking and other addictive behaviors.