Effect of dopamine D-1 and D-2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo.
The effect of the dopamine (DA) D-1 agonist SKF 38393, the D-2 agonist LY 171555 and the mixed D-1/D-2 agonist apomorphine on striatal DA release and metabolism was tested in vivo using an intracerebral dialysis method in halothane-anaesthetized rats. The specificity of responses to these agonists was tested using the selective DA antagonists SCH 23390 (D-1) and sulpiride (D-2). Both LY 171555, 0.01 mg/kg, and SKF 38393, 10 mg/kg, reduced levels of DA in striatal perfusates. Neither SCH 23390, 0.5 and 5 mg/kg, nor sulpiride, 10 mg/kg, affected levels of DA in striatal perfusates, but 250 mg/kg sulpiride caused a DA increase. The decrease of DA levels induced by LY 171555 (0.01 mg/kg) was prevented by pretreatment with sulpiride (10 mg/kg) but not SCH 23390 (0.5 mg/kg). In comparison, pretreatment with SCH 23390 (0.5 mg/kg) completely inhibited the reduction of DA induced by SKF 38393 (10 mg/kg) while sulpiride (10 mg/kg) was without effect. Apomorphine (0.05 mg/kg) also decreased DA in striatal perfusates and this action was partially inhibited by both SCH 23390 (0.5 mg/kg) and sulpiride (10 mg/kg). Levels of the DA metabolite DOPAC in striatal perfusates also significantly decreased following LY 171555 (0.01 mg/kg) and apomorphine (0.05 mg/kg) but not SKF 38393 (10 mg/kg). The antagonist SCH 23390, in a dose, 0.5 mg/kg, that alone did not increase levels of DOPAC, inhibited the reduction of DOPAC induced by both LY 171555 and apomorphine. Sulpiride, 10 mg/kg, caused a marked increase in striatal DOPAC and this was not affected by a subsequent injection of LY 171555, SKF 38393 or apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D001058:Apomorphine; D004298:Dopamine