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 485, 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.
Zhang
M
M
Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark 07102.
Creese
I
I
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D015259:Dopamine Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004873:Ergolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*
D015259:Dopamine Agents; D004873:Ergolines; D016376:Oligonucleotides, Antisense; D017448:Receptors, Dopamine D2; D019257:Quinpirole