The behavioural and neurochemical profile of the putative dopamine D-3 receptor agonist, (+)-PD 128907, in the rat

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 mu g/kg, s.c.) a response which was comparable with the non-selective D-2/3 receptor agonist apomorphine (ED(50) = 13 +/- 1.6 mu g/kg, s.c.). In addition (+)-PD 128907 impaired prepulse inhibition of the acoustic startle response, with significant effects observed at doses of 30 mu g/kg when appropriate prepulse intensities were used. Higher doses reversed gamma-butyrolactone-induced catecholamine synthesis (ED(50) = 95 +/- 22 and 207 +/- 37 mu g/kg in accumbens and striatum respectively) and induced yawning (100-300 mu g/kg), penile grooming (30-1000 mu g/kg) and sniffing (greater than or equal to 300 mu g/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. Copyright (C) 1996 Elsevier Science Ltd.