EVIDENCE FOR SELECTIVE INVOLVEMENT OF DOPAMINE D-1 RECEPTORS OF THE VENTRAL TEGMENTAL AREA IN THE BEHAVIORAL SENSITIZATION INDUCED BY INTRA-VENTRAL TEGMENTAL AREA INJECTIONS OF D-AMPHETAMINE

The induction of behavioral sensitization to D-amphetamine (AMPH) is k nown to result at least in part from an action of the drug in the vent ral tegmental area (VTA), which contains the dopamine (DA) A10 cell bo dies. To specify the cellular mechanisms through which AMPH acts in th e VTA and leads to behavioral sensitization after repeated intra-VTA i njections, the involvement of VTA DA D-1 and D-2 and serotonin, recept ors in this phenomenon was investigated in independent experiments. Th e results reported here confirm that repeated intra-VTA AMPH injection s (four injections of 5 mu g/0.5 mu l every other day) induce behavior al sensitization, as revealed by the potentiation of the locomotor res ponse to peripheral challenges with AMPH (0.5 mg/kg) 4 or 15 days afte r treatment. This behavioral sensitization induced by intra-VTA admini stration of AMPH cross-reacts with morphine (1 mu g/0.5 mu l) administ ered into the VTA 7 days after treatment. We demonstrated that the D-1 receptor antagonist +)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl- 1 H-3-benzazepin-7-ol (0, 0.01, 0.1 and 1 mu g/ 0.5 mu l) coadminister ed in the VTA with AMPH dose-dependently prevents the behavioral sensi tization to peripheral AMPH challenges (at either 4 or 15 days after t reatment) as well as the cross-sensitization with intra-VTA morphine. Neither DA D-2 nor serotonin(2) receptor blockade, using sulpiride (10 mu g/0.5 mu l) and ketanserin (1 mu g/0.5 mu l), respectively, had an y effect on the induction of behavioral sensitization. In conclusion, these results demonstrate the selective involvement of VTA DA D-1 rece ptors in the process by which AMPH acts in the VTA to induce behaviora l sensitization.