Distinct roles of dopamine D2 receptors in dorsal and ventral striatum on motor and drug-related behaviors

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAAA	NEURO/BEHAV/SENSYS-12

Authors

• A.R. Kaplan
• T. Doyle
• E. Casey
• R.B. Free
• D.R. Sibley
• M. Rubenstein
• V.A. Alvarez

Abstract

This project utilized a multi-pronged approach to study the role of striatal D2Rs in motor and drug-related behaviors, considering the effects of both a life-long reduction of D2R expression in indirect-pathway medium spiny neurons (iMSNs) and an acute reduction of D2R expression in the ventral striatum (NAc). A Cre-loxP system induced life-long knockdown of D2R expression in iMSNs (MSN-D2 KD). A 30% reduction of striatal D2Rs was confirmed by qPCR and radioligand binding. In MSN-D2 KD mice, exploratory locomotion, acute locomotor response to cocaine, and locomotor sensitization to cocaine were normal, but rotarod performance was impaired. To acutely reduce D2R expression in the NAc, viral vectors expressing Cre recombinase under a strong promoter were stereotaxically injected into the NAc of mice with floxed Drd2 genes. Cre-injected mice displayed markedly reduced (85%) NAc Drd2 mRNA levels, showed reduced locomotion in novel and home cage environments, and had a blunted acute locomotor response to cocaine. Despite these impairments, mice lacking NAc D2R showed locomotor sensitization to cocaine and normal motor learning when trained on the rotarod. These findings implicate the importance of NAc D2Rs in explorative behaviors and acute responses to cocaine, and of D2Rs in the dorsal striatum for motor learning.

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