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

Sep 29, 1999Neuroscience

Dopamine D1 and D2 activators affect movement differently depending on brain area

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Abstract

0.3–1 microg of the D1 agonist SKF 38393 increased locomotor activity in the ventral pallidum.

3 microg of SKF 38393 had no effect on locomotion in the ventral pallidum.
3 microg of the D2 agonist quinpirole suppressed locomotion, while lower doses had no effect.
A combination of 0.3 microg SKF 38393 and quinpirole increased locomotor activity more than quinpirole alone but not significantly more than SKF 38393 alone.
Injections of SKF 38393 into the anterior ventral pallidum increased activity, while injections into the posterior ventral pallidum decreased it.
In the nucleus accumbens, doses from 0.3 to 3 microg of SKF 38393 dramatically increased locomotor activity, while quinpirole had a moderate effect.
Sensitized locomotor responses were observed in rats previously treated with SKF 38393 when given subsequent doses of SKF 38393, quinpirole, or their mixture.

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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 D1 and D2 receptors in evoking locomotor activity with those in the nucleus accumbens. The D1 agonist SKF 38393 and the D2 agonist quinpirole hydrochloride (0.3-3 microg/ 0.5 microl) were bilaterally injected into ventral pallidum or nucleus accumbens through pre-implanted cannulae. In the ventral pallidum, 0.3-1 microg SKF 38393 increased locomotor activity while 3 microg had no effect; 3 microg quinpirole suppressed locomotion while 0.3-1 microg had no effect. Locomotor activity induced by an equigram (0.3 microg) mixture of SKF 38393 and quinpirole, while significantly higher than that induced by 0.3 microg quinpirole was not significantly higher than that induced by 0.3 microg SKF 38393 alone. At the 3 microg dose, SKF 38393 injections into anterior ventral pallidum increased activity; injections into posterior ventral pallidum decreased activity. In the nucleus accumbens, 0.3-3 microg 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 microg) 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 D1 and D2 receptor activation may facilitate each other to induce a synergistic effect on locomotor activity, ventral pallidal D1 and D2 receptors may be located on different neurons and coupled with different, if not opposite, behavioral output.

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

Abstract

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