The D3 receptor is thought to play a role in reinforcement pathways because it is expressed in high levels within the mesolimbic dopaminergic system and, more specifically, the nucleus accumbens shell. (+)-PD 128907 HCl is a dopaminergic agonist with a range of in vitro D3 selectivity[1]. Low doses of (+)-PD 128907 reduced spontaneous locomotor activity in the rat (ED50 = 13 ± 3 μg/kg, s.c.) a response which was comparable with the non-selective D2,3 receptor agonist apomorphine (ED50 = 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 of (+)-PD 128907 HCl reversed gamma-butyrolactone-induced catecholamine synthesis (ED50 = 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 (> or = 300 μg/kg). In addition, the observation that (+)-PD 128907 disrupts prepulse inhibition, a phenomenon which is also impaired in schizophrenic subjects[2].
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