The D2-like dopamine receptor agonist quinpirole microinjected into the ventral pallidum dose-dependently inhibits the VTA and induces place aversion.

Péczely, László and Ollmann, Tamás and László, Kristóf and Lénárd, László and Grace, Anthony A. (2022) The D2-like dopamine receptor agonist quinpirole microinjected into the ventral pallidum dose-dependently inhibits the VTA and induces place aversion. INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 25 (7). pp. 590-599. ISSN 1461-1457

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Abstract

The ventral pallidum (VP) is a dopaminoceptive forebrain structure regulating the ventral tegmental area (VTA) dopaminergic population activity. We have recently demonstrated that in the VP, the D2-like DA receptor (D2R) agonist quinpirole dose-dependently facilitates memory consolidation in inhibitory avoidance and spatial learning. According to our hypothesis, quinpirole microinjected into the VP can modulate the VTA DAergic activity and influence motivation and learning processes of rats.Quinpirole was microinjected at three different doses into the VP of male rats, controls received vehicle. Single unit recordings were employed to assess VTA DAergic activity. To investigate the possible reinforcing or aversive effect of quinpirole in the VP, the conditioned place preference (CPP) paradigm was used.Our results showed that intra-VP quinpirole microinjection regulates VTA DAergic neurons according to an inverted U-shaped dose-response curve. The largest dose of quinpirole decreased the population activity and strongly reduced burst activity of the DAergic neurons in the first hour after its application. In contrast, the two smaller doses increased DA population activity, but their effect started with a delay, one hour after their microinjection. The CPP experiments revealed that the largest dose of quinpirole in the VP induces place aversion in the rats. Furthermore, the largest dose of quinpirole induced an acute locomotor activity reduction, while the medium dose led to a long-duration increase in locomotion.In summary, quinpirole dose-dependently regulates VTA DAergic activity as well as the motivation and motor behavior of the rats at the level of the VP.

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