Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin.
Intracerebroventricular (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3H]raclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (+/-)-7-hydroxy-dipropyl-aminotetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both post- and presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.
Wanderoy
M H
MH
CNS Preclinical R&D, Astra Arcus AB, Södertälje, Sweden.
Westlind-Danielsson
A
A
Ahlenius
S
S
D000818:Animals; D002552:Cerebral Ventricles; D005576:Colforsin / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012457:Salicylamides / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D015854:Up-Regulation
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D005576:Colforsin; D020891:Raclopride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin