THE PUTATIVE DOPAMINE D-3 AGONIST, 7-OH-DPAT, REDUCES DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS AND ELECTRICAL SELF-STIMULATION TO THE VENTRAL TEGMENTUM

The present experiments were designed to test further the idea that 7- OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin), a putative dopami ne (DA) D-3 agonist, has effects at DA autoreceptors to reduce intracr anial DA levels and to reduce behaviours that are DA-dependent. Rats w ere trained to respond on a self-stimulation protocol for electrical s timulation to the ventral tegmental area (VTA). Each press of a lever delivered a 0.5 s train of square wave, 1.5 ms duration, 100 Hz, 90-12 0 mA stimulation. Systemic administration of 7-OH-DPAT at 0.01-0.3 mg/ kg i.p., quickly dose-dependently reduced responding. Electrical stimu lation using similar parameters to those that supported self-stimulati on were then applied to the VTA of anaesthetized rats. Fast cyclic vol tammetry (FCV) revealed that this stimulation released DA in the nucle us accumbens (NAC). 7-OH-DPAT i.p. (0.1-3.0 mg/kg) quickly and potentl y reduced the size of the DA-generated voltammetric signal. This effec t of 0.3 mg/kg 7-OH-DPAT was not blocked by sulpiride (60 mg/kg, i.p.) a D-2-specific antagonist that may preferentially block D-2 autorecep tors. These data are discussed with reference to the possibility that 7-OH-DPAT reduces the release of dopamine in the NAC, at D-3, but not at D-2, autoreceptors and that this in turn may reduce the rewarding e ffect of VTA stimulation.