Effect of dopamine D-1 and D-2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1986-10, Vol.334 (2), p.117-124
• Main Authors: ZETTERSTROM, T, SHARP, T, UNGERSTEDT, U
• Format: Article
• Language: English
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Animals; Apomorphine - pharmacology; Applied sciences; Benzazepines - pharmacology; Biological and medical sciences; Catecholaminergic system; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dialysis; Dopamine - metabolism; Dopamine Antagonists; Ergolines - pharmacology; Exact sciences and technology; Male; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Other techniques and industries; Pharmacology. Drug treatments; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine - drug effects; Receptors, Dopamine - metabolism; Receptors, Dopamine D1; Receptors, Dopamine D2; Sulpiride - pharmacology
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00505810

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.