THE BEHAVIORAL AND NEUROCHEMICAL PROFILE OF THE PUTATIVE DOPAMINE D-3RECEPTOR AGONIST, (-PD-128907, IN THE RAT())

The functional relevance of the dopamine D-3 receptor is still unresol ved, largely because of the absence of selective D-3 receptor ligands. In the present study we have examined the in vivo profile of (+)-PD 1 28907, a potent and functionally selective D-3 receptor agonist. Low d oses of (+)-PD 128907 reduced spontaneous locomotor activity in the ra t (ED(50) = 13 +/- 3 mu g/kg, s.c.) a response which was comparable wi th 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 inh ibition of the acoustic startle response, with significant effects obs erved at doses of 30 mu g/kg when appropriate prepulse intensities wer e used. Higher doses reversed gamma-butyrolactone-induced catecholamin e synthesis (ED(50) = 95 +/- 22 and 207 +/- 37 mu g/kg in accumbens an d 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 r equired to produce maximal effects. In contrast to apomorphine, howeve r, (+)-PD 128907 failed to induce intense stereotyped licking and biti ng 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 s uggested. In addition, the observation that (+)-PD 128907 disrupts pre pulse inhibition, a phenomenon which is also impaired in schizophrenic subjects, may indicate the pathological importance of this receptor s ubtype. Copyright (C) 1996 Elsevier Science Ltd.