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 degrees 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 degrees C, U69,593 at 52 degrees C, and bremazocine at 50 degrees 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.