Activation of D2 autoreceptors alters cocaine-induced locomotion and slows down local field oscillations in the rat ventral tegmental area

作者：Koulchitsky Stanislav; Delairesse Charlotte; Beeken Thom; Monteforte Alexandre; Dethier Julie; Quertemont Etienne; Findeisen Rolf; Bullinger Eric; Seutin Vincent^*

来源：Neuropharmacology, 2016, 108: 120-127.

DOI：10.1016/j.neuropharm.2016.04.034

• Stereotypies
• Local field potential
• Ventral tegmental area
• Cocaine
• Quinpirole

Psychoactive substances affecting the dopaminergic system induce locomotor activation and, in high doses, stereotypies. Network mechanisms underlying the shift from an active goal-directed behavior to a "seemingly purposeless" stereotypic locomotion remain unclear. In the present study we sought to determine the relationships between the behavioral effects of dopaminergic drugs and their effects on local field potentials (LFPs), which were telemetrically recorded within the ventral tegmental area (VTA) of freely moving rats. We used the D2/D3 agonist quinpirole in a low, autoreceptor-selective (0.1 mg/kg, i.p.) and in a high (0.5 mg/kg, i.p.) dose, and a moderate dose of cocaine (10 mg/kg, i.p.). In the control group, power spectrum analysis revealed a prominent peak of LFP power in the theta frequency range during active exploration. Cocaine alone stimulated locomotion, but had no significant effect on the peak of the LFP power. In contrast, co-administration of low dose quinpirole with cocaine markedly altered the pattern of locomotion, from goal-directed exploratory behavior to recurrent motion resembling loco motor stereotypy. This behavioral effect was accompanied by a shift of the dominant theta power toward a significantly lower (by similar to 15%) frequency. High dose quinpirole also provoked an increased locomotor activity with signs of behavioral stereotypies, and also induced a shift of the dominant oscillation frequency toward the lower range. These results demonstrate a correlation between the LFP oscillation frequency within the VTA and a qualitative aspect of locomotor behavior, perhaps due to a variable level of coherence of this region with its input or output areas.

• 出版日期2016-9