Modulatory effects of dopamine D3/2 agonists on kappa opioid-induced antinociception and diuresis in the rat

Abstract.

Rationale: The dopamine (DA) D3/2 agonist 7-OH-DPAT has been shown to attenuate the behavioral effects of the mu agonist morphine as well as the development of morphine tolerance. Objectives: To evaluate the effects of DA D3/2 agonists [7-OH-DPAT, (+)-PD128,907, quinelorane, (-)-quinpirole], a D1 agonist (SKF38393), a D1 antagonist [(+)-SCH23390], a DA antagonist (spiperone), and an indirect DA agonist (cocaine) on the antinociceptive effects of kappa agonists (spiradoline, U69,593, bremazocine) as well as the effects of D3/2 agonists on the diuretic effects of spiradoline. Methods: Antinociception was determined using a warm water (50–55°C) tail-withdrawal procedure and urine output was collected over a 2-h interval. Results: The antinociceptive effects produced by the kappa agonists varied with the intensity of the nociceptive stimulus (water), as maximal or near maximal effects were obtained with spiradoline at 55°C, U69,593 at 52°C, and bremazocine at 50°C water. 7-OH-DPAT produced a dose-dependent attenuation of the antinociceptive effects of spiradoline, U69,593, and bremazocine. Spiperone completely reversed the effects of 7-OH-DPAT on spiradoline antinociception. (+)-PD128,907 and quinelorane, but not (-)-quinpirole or the other DAergic agents examined, attenuated the antinociceptive effects of spiradoline in a dose- and time-dependent manner. The diuretic effects of spiradoline were attenuated by 7-OH-DPAT, (+)-PD128,907, quinelorane, and (-)-quinpirole, and this attenuation was reversed by spiperone. Conclusions: The present study demonstrated that some D3/2 agonists can modulate both the antinociceptive and diuretic effects of kappa agonists. These modulatory actions are similar to those obtained against the effects of mu agonists.