Antisense oligodeoxynucleotide reduces brain dopamine D2 receptors: Behavioral correlates

Abstract Intraventricular infusion of an antisense oligodeoxynucleotide corresponding to the rat dopamine D 2 receptor mRNA reduced rat striatal D 2 receptors by 48%, as measured by homogenate binding assays, while D 1 , muscarinic, and serotonin 5-HT 2 receptors were unaffected. D 2 receptor autoradiography indicated a homogeneous down-regulation of about 50% throughout the striatum and over 70% in the nucleus accumbens. A random oligodeoxynucleotide failed to affect either striatal D 2 or D 1 receptor density. The antisense treatment inhibited the D 2 receptor agonist quinpirole-induced locomotor activation, without altering grooming behavior induced by SKF38393, a D 1 receptor agonist. Antisense treatment also elicited catalepsy and reduced spontaneous locomotor activity.