DOPAMINE RESPONSES TO REWARD AND REWARD-RELATED CUES ARE ALTERED IN A MOUSE THAT OVEREXPRESSES DOPAMINE D2 RECEPTORS IN THE STRIATUM

JEONG, NURI; SIMPSON, ELEANOR; BELLO, ESTEFANÍA; GOLDMAN, OLIVIA

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

SOCIEDAD ARGENTINA DE INVESTIGACION EN NEUROCIENCIAS

Dopamine (DA) hypothesis has been the leading pathoetiologic theory of schizophrenia (SZ) for many decades. Striatal DA hyperfunction has been consistently linked to psychosis. However, more recent studies show a generalized DA deficit including cortical areas and extrastriatal regions not previously considered to be hypodopaminergic in SZ such as the ventral striatum, with increase presynaptic DA activity restricted to the associative striatum. DA neurons compute reward prediction errors proposed to serve as the basic process underlying associative learning in classical and instrumental conditioning procedures. Patients show deficits in reinforcement learning including reward anticipation, reversal learning, probabilistic learning and reward representation. Such deficits, part of the cognitive and negative symptoms, do not improve with antipsychotic medication and their severity determines patient´s prognosis. To understand DA dysregulation in SZ, we use fast-scan cyclic votammetry to monitor DA release in the nucleus accumbens of a mouse model for cognitive and negative symptoms of SZ that presents a 15% increase in striatal D2 receptor levels as has been observed in patients with SZ. We hypothesize that striatal D2R overexpression induces changes in DA release that are responsible for the behavioral deficits observed in the mice. We show DA release to be altered and to correlate to altered behavior in order to explain the observed SZ-like phenotype.