ANTISENSE OLIGODEOXYNUCLEOTIDE REDUCES BRAIN DOPAMINE-D2 RECEPTORS - BEHAVIORAL-CORRELATES

Intraventricular infusion of an antisense oligodeoxynucleotide corresponding to the rat dopamine D2 receptor mRNA reduced rat striatal D2 receptors by 48%, as measured by homogenate binding assays, while D1, muscarinic, and serotonin 5-HT2 receptors were unaffected. D2 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 D2 or D1 receptor density. The antisense treatment inhibited the D2 receptor agonist quinpirole-induced locomotor activation, without altering grooming behavior induced by SKF38393, a D1 receptor agonist. Antisense treatment also elicited catalepsy and reduced spontaneous locomotor activity.