Effects of the dopamine D3-and autoreceptor preferring antagonist (???)-DS121 on locomotor activity, conditioned place preference and intracranial self-stimulation in the rat

Abstract

The phenylpiperidine (-)-DS121 (S-(-)-3-(-3-cyanophenyl)-N-n-propyl piperidine) represents a new class of weak stimulants acting as preferential dopamine autoreceptor antagonists. (-)-DS121 dose-dependently increases locomotor activity over a wide dose range in rats after systemic administration. (-)-DS121 also exhibits a weak preference for the D3 receptor in in vitro binding studies. The relevance of this D3 preference is not clear and it is not known whether the D3 receptor site influences reward mechanisms. The present results showed that (-)-DS121 induced place conditioning in the dose range 3.3-13.3mg/kg s.c. as did d-amphetamine (0.25-4.0mg/kg, s.c.). However, in contrast to d-amphetamine, (-)-DS121 failed to facilitate infracranial self-stimulation in the dose range that produced place conditioning. Local bilateral infusion of (-)-DS121 (0.05-53.0µg/side) into the nucleus accumbens or ventral tegmental area did not produce locomotor stimulation. A weak but significant increase in locomotor activity was detected after bilateral infusion of (-)-DS121 (66.3µg/side) into the lateral ventricles. This study suggests that the behavioural stimulant (-)-DS121 does not possess strong reward-facilitating properties and that local application in either the terminal or somatodendritic regions of the mesolimbic pathway does not produce the same degree of locomotor activity as seen after systemic administration.