27.2 Selective Overexpression of EAAT3 in Midbrain Dopamine Neurons Leads to Increased OCD-like Behaviors

Abstract

OCD is a severe, chronic condition that affects 2% to 3% of the population. Genetic findings have pointed to SLC1A1, encoding the neuronal glutamate transporter EAAT3/EAAC1, with evidence suggesting that increased expression may contribute to risk. We previously reported that a loss of Slc1a1 in mice leads to decreased amphetamine (AMPH)-induced dopamine (DA) release, locomotion, and stereotypic movements, as well as decreased SKF-38393 (D1-agonist)-induced grooming behavior. Viral rescue of midbrain Slc1a1 expression partially restored the behavioral response to AMPH, suggesting an impact on DA neuron function. Here, to test more directly the developmental impact of DA neuron EAAT3 overexpression on compulsive-like behaviors, we generated mice with DA neuron–selective overexpression of EAAT3. We hypothesized that increased expression in DA neurons would lead to increased OCD-like behaviors.