EFFECTS OF THE DOPAMINE D3-AND AUTORECEPTOR PREFERRING ANTAGONIST (-)-DS121 ON LOCOMOTOR-ACTIVITY, CONDITIONED PLACE PREFERENCE AND INTRACRANIAL SELF-STIMULATION IN THE RAT

The phenylpiperidine (-)-DS121 (S-(-)-3-(-3-cyanophenyl)-N-n-propyl pi peridine) represents a new class of weak stimulants acting as preferen tial dopamine autoreceptor antagonists. (-)-DS121 dose-dependently inc reases locomotor activity over a ,vide dose range in rats after system ic administration. (-)-DS121 also exhibits a weak preference for the D 3 receptor in in vitro binding studies. The relevance of this D3 prefe rence is not clear and it is not known whether the D3 receptor site in fluences reward mechanisms. The present results showed that (-)-DS121 induced place conditioning in the dose range 3.3-13.3 mg/kg s.c. as di d d-amphetamine (0.25-4.0 mg/kg, s.c.). However, in contrast to d-amph etamine, (-)-DS121 failed to facilitate intracranial self-stimulation in the dose range that produced place conditioning. Local bilateral in fusion of(-)-DS121 (0.05-53.0 mu g/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 bila teral infusion of(-)-DS121 (66.3 mu g/side) into the lateral ventricle s. This study suggests that the behavioural stimulant (-)-DS121 does n ot possess strong reward-facilitating properties and that local applic ation in either the terminal or somatodendritic regions of the mesolim bic pathway does not produce the same degree of locomotor activity as seen after systemic administration.