Anticonflict effects of low doses of the dopamine agonist apomorphine in the rat.

The effects of low, "autoreceptor" doses (3.13-100 micrograms/kg, SC) of the dopamine (DA) agonist apomorphine were investigated in a modified Vogel's conflict paradigm. The compound was found to exert a marked, dose-dependent increase in the number of shocks taken in the conflict situation (maximum: approximately 230% of control responding, obtained at 12.5 micrograms/kg), thus indicating an anxiolytic action. However, the dose-response curve was biphasic, inversely U-shaped, with the highest dose tried actually suppressing the punished response rate to below control levels. Neither low- nor high-dose apomorphine modified the rats' drinking "motivation" (glucose intake after 48 hr of water deprivation). On the other hand, while unaltered by 12.5 micrograms/kg, the pain threshold tended to be lowered by 100 micrograms/kg. It is suggested that the anxiolytic-like action of apomorphine might be due to central DA autoreceptor stimulation, possibly in limbic/cortical forebrain regions. The conflict-promoting effect seen at 100 micrograms/kg is likely related to the concomitantly elicited hyperalgesia. The possibility of developing novel DA-modulating agents for the treatment of anxiety is raised.