Repeated administration of (-)sulpiride and SCH 23390 differentially up-regulate D-1 and D-2 dopamine receptor function in rat mesostriatal areas but not in cortical-limbic brain regions.
We studied the possible functional modifications of both D-1 and D-2 dopamine (DA) receptor subtypes following repeated administration of DA antagonists that act selectively on a single class of DA receptors. The functional state of D-1 and D-2 DA receptors in particular was evaluated by measuring SKF 82526-stimulated and bromocriptine-inhibited adenylate cyclase activity in different brain regions of rats treated with saline, SCH 23390, or (-)sulpiride for 21 days. The results indicate that chronic blockade of D-1 DA receptors in striatum, nucleus accumbens, and substantia nigra by SCH 23390 induced up-regulation of the D-1 receptors without changing the functional activity of D-2 receptors. Likewise, chronic blockade of D-2 DA receptors by (-)sulpiride caused up-regulation of D-2 but not D-1 DA receptors in striatum, nucleus accumbens, substantia nigra and pituitary. SCH 23390 or (-)sulpiride did not modify the functional activity of either D-1 or D-2 DA receptors located in frontal cortex and hippocampus. In conclusion, these results indicate that chronic treatment with selective D-1 or D-2 DA receptor blockers induces a receptor-specific up-regulation which involves the DA receptors located in the nigrostriatal system and pituitary but not those in the limbic-cortical areas.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D001971:Bromocriptine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D018818:Fenoldopam; D008032:Limbic System / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014150:Antipsychotic Agents; D001552:Benzazepines; D011954:Receptors, Dopamine; D014665:Vasodilator Agents; D001971:Bromocriptine; D013469:Sulpiride; D000262:Adenylyl Cyclases; D018818:Fenoldopam