The role of ventral tegmental dopamine neurons in locomotor sensitization following quinpirole or (+)-amphetamine : Ex vivo voltammetric evidence

Abstract

Behavioural sensitization to the locomotor stimulating effects of (+)-amphetamine or quinpirole was induced in rats by intermittent drug administration. Following expression of sensitization, locomotor activity scores on day 9 were: vehicle 87 +/- 9, (+)-amphetamine 1441 +/- 227 and quinpirole 2078 +/- 214. Electrically stimulated dopamine release was measured on day 12 in ventral tegmental slices using fast cyclic voltammetry. Dopamine release was significantly elevated in the (+)-amphetamine- and quinpirole-treated groups when compared to vehicle-treated controls over a wide range of stimulation frequencies (5-200 Hz) and pulses (1-200). Quinpirole (1 mu M) in the perfusion fluid attenuated dopamine release following 40-pulse, 200-Hz electrical stimulation, by 31.6 +/- 2.8% in the ventral tegmental area of the vehicle-treated group, by 14.8 +/- 5.6% in the (+)-amphetamine-treated group and 8 +/- 7.3% in the quinpirole-treated group. This study shows that dopamine release is increased in the ventral tegmental area following sensitization with either a direct or indirectly acting dopamine agonist. The findings that dopamine release was elevated at all stimulation frequencies in sensitized animals, and that quinpirole only attenuated this release at the highest stimulation frequency, would suggest that in addition to D-2 autoreceptor subsensitivity, other mechanisms contribute to the enhanced release of dopamine in these animals.