Dopamine D-1/D-2 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 i n evoking locomotor activity with those in the nucleus accumbens. The D-1 a gonist 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 accumbe ns 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 quinp irole suppressed locomotion while 0.3-1 mu g had no effect. Locomotor activ ity 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. I n the nucleus accumbens, 0.3-3 mu g SKF 38393 dramatically increased locomo tor 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 locomot or 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. More over, rats that had previously received SKF 38393 developed a sensitized lo comotor response to subsequent SKF 38393, quinpirole or the mixture of thes e two drugs. The difference in locomotor response to dopamine agonists between the ventr al pallidum and nucleus accumbens is consistent with electrophysiological e vidence collected at these two sites. These findings suggest that, unlike t he nucleus accumbens, where D-1 and D-2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pa llidal D-1 and D-2 receptors may be located on different neurons and couple d with different, if not opposite, behavioral output. (C) 1999 IBRO. Publis hed by Elsevier Science Ltd.