DOPAMINE D-3 (AUTO) RECEPTORS INHIBIT DOPAMINE RELEASE IN THE FRONTAL-CORTEX OF FREELY MOVING RATS IN-VIVO

In freely moving rats, the novel, selective dopamine (DA) D-3 receptor agonist PD 128,907 dose-dependently [effective dose (ED(25)) = 0.07 m g/kg, s.c.] reduced dialysate levels of DA in the frontal cortex, a st ructure innervated by the ventral tegmental area (VTA). This action of PD 128,907 (0.16 mg/kg, s.c.) was abolished by a selective DA D-3 rec eptor antagonist S 14297 (1.25 mg/kg, s.c.), which alone did not modif y levels of DA. In contrast to S 14297, its inactive distomer, S 17777 , did not modify the actions of PD 128,907. In addition, PD 128,907 do se-dependently and potently inhibited the firing rate of VTA-localized neurons in anesthetized rats (ED(50) = 0.001 mg/kg, i.v.). S 14297, b ut not S 17777, completely reversed the actions of PD 128,907 (0.005 m g/kg, i.v.) with a 50% inhibitory dose of 0.03 mg/kg, i.v. and did not itself significantly modify the firing rate. In conclusion, these dat a provide the first direct evidence that DA D-3 (auto)receptors modula te (inhibit) the release of DA in the frontal cortex.