Decreased striatal dopamine efflux after intrastriatal application of benzazepine-class D1 agonists is not mediated via dopamine receptors

Jun 19, 2001Brain research bulletin

Reduced dopamine release in movement areas after applying benzazepine D1 activators is not caused by dopamine receptors

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Abstract

Both the partial D1 agonist (+/-)-SKF 38393 and the full D1 agonist (+/-)-SKF 82958 significantly reduced striatal dopamine efflux during intrastriatal application.

The reduction in striatal dopamine efflux was observed with both 10 and 100 microM doses of (+/-)-SKF 82958.
Intrastriatal application of S(-)-SKF 38393 did not decrease striatal dopamine, indicating selective receptor activity.
Local application of the D1 antagonist R(+)-SCH 23390 and the selective D2 antagonist raclopride did not block the effects of (+/-)-SKF 82958.
Haloperidol, a less selective D2 antagonist, prevented the decrease in dopamine efflux during (+/-)-SKF 82958 application.
The findings suggest that the decrease in striatal dopamine efflux from benzazepine-class D1 agonists is receptor-mediated, but not through D1 or D2 receptors.

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Previous pharmacological studies have reported that striatal dopamine efflux is negatively modulated not only by presynaptic D2 dopamine autoreceptors but also by striatal D1 dopamine receptors. The present experiments employed in vivo microdialysis to further examine the ability of widely used benzazepine-class D1 agonists to modulate striatal dopamine efflux. In the present study, both the partial D1 agonist (+/-)-SKF 38393 (10 microM) and the full D1 agonist (+/-)-SKF 82958 (10 and 100 microM) significantly reduced striatal dopamine efflux during intrastriatal application. Intrastriatal application of the less active enantiomer, S(-)-SKF 38393 (10 microM) did not decrease striatal dopamine suggesting a selective receptor-mediated mode of action of (+/-)-SKF 38393. Additional experiments were conducted with the full D1 agonist (+/-)-SKF 82958 in order to characterize the receptor(s) mediating the observed decrease in dopamine efflux. Neither local application of the D1 antagonist R(+)-SCH 23390 (100 microM) nor local application of the selective D2 antagonist raclopride (5 microM) blocked the ability of (+/-)-SKF 82958 (10 microM) to decrease striatal dopamine efflux. However, intrastriatal application of the less selective D2 antagonist haloperidol (1 microM) did prevent the decrease in striatal dopamine efflux observed during intrastriatal (+/-)-SKF 82958 application. The present data suggest that the ability of intrastriatally applied benzazepine-class D1 agonists to decrease striatal dopamine efflux is receptor-mediated, but this action apparently is not mediated at D1 or D2 receptors. There is therefore no indication for an intrastriatal population of D1 receptors capable of modulating dopamine efflux.

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Decreased striatal dopamine efflux after intrastriatal application of benzazepine-class D1 agonists is not mediated via dopamine receptors

Abstract

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