Dopamine D1/D2 agonists injected into nucleus accumbens and ventral pallidum differentially affect locomotor activity depending on site

Ventral pallidal dopamine has been recently shown to play an important role in psychostimulant reward and locomotor activation. The aim of the present study was to compare the roles of ventral pallidal D-1 and D-2 receptors in evoking locomotor activity with those in the nucleus accumbens. The D-1 agonist SKF 38393 and the D-2 agonist quinpirole hydrochloride (0.3-3 mu g/0.5 mu l) were bilaterally injected into ventral pallidum or nucleus accumbens through pre-implanted cannulae. In the ventral pallidum, 0.3-1 mu g SKF 38393 increased locomotor activity while 3 mu g had no effect; 3 mu g quinpirole suppressed locomotion while 0.3-1 mu g had no effect. Locomotor activity induced by an equigram (0.3 mu g) mixture of SKF 38393 and quinpirole, while significantly higher than that induced by 0.3 mu g quinpirole was not significantly higher than that induced by 0.3 mu g SKF 38393 alone. At the 3 mu g dose, SKF 38393 injections into anterior ventral pallidum increased activity; injections into posterior ventral pallidum decreased activity. In the nucleus accumbens, 0.3-3 mu g SKF 38393 dramatically increased locomotor activity while quinpirole moderately increased locomotion. In the group that had previously received the full quinpirole dose range, injection of the equigram (0.3 mu g) mixture of SKF 38393 and quinpirole induced locomotor activation which was higher than that induced by either drug alone or by the addition of the effect of each drug alone, i.e. synergy occurred. Moreover, rats that had previously received SKF 38393 developed a sensitized locomotor response to subsequent SKF 38393, quinpirole or the mixture of these two drugs. The difference in locomotor response to dopamine agonists between the ventral pallidum and nucleus accumbens is consistent with electrophysiological evidence collected at these two sites. These findings suggest that, unlike the nucleus accumbens, where D-1 and D-2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pallidal D-1 and D-2 receptors may be located on different neurons and coupled with different, if not opposite, behavioral output. (C) 1999 IBRO. Published by Elsevier Science Ltd.