The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat.

Abstract The functional relevance of the dopamine D 3 receptor is still unresolved, largely because of the absence of selective D 3 receptor ligands. In the present study we have examined the in vivo profile of (+)-PD 128907, a potent and functionally selective D 3 receptor agonist. Low doses of (+)-PD 128907 reduced spontaneous locomotor activity in the rat (ED 50 = 13 ± 3 μg/kg, s.c.) a response which was comparable with the non-selective D 2 3 receptor agonist apomorphine (ED 50 = 13 ± 1.6 μg/kg, s.c.). In addition (+)-PD 128907 impaired prepulse inhibition of the acoustic startle response, with significant effects observed at doses of 30 μg/kg when appropriate prepulse intensities were used. Higher doses reversed γ-butyrolactone-induced catecholamine synthesis (ED 50 = 95 ± 22 and 207 ± 37 μg/kg in accumbens and striatum respectively) and induced yawning (100–300 μg/kg), penile grooming (30–1000 μg/kg) and sniffing (⩾ 300 μg/kg) although doses 3- to 10-fold greater than apomorphine were required to produce maximal effects. In contrast to apomorphine, however, (+)-PD 128907 failed to induce intense stereotyped licking and biting in the rat. In view of the potency and selectivity of (+)-PD 128907 for the D 3 receptor, a role in the control of locomotor activity is suggested. In addition, the observation that (+)-PD 128907 disrupts prepulse inhibition, a phenomenon which is also impaired in schizophrenic subjects, may indicate the pathological importance of this receptor subtype.