Dopamine D3 receptor agonists produce similar decreases in body temperature and locomotor activity in D3 knock-out and wild-type mice

The function of the dopamine (DA) D-3 receptor, a member of the D2-like family, has not been firmly established. It has been reported that the potency of DA receptor agonists in producing hypothermia and hypolocomotion in rodents correlates more strongly with the in vitro affinity for, or potency (mitogenesis test) at the D-3 than the D-2 subtype. In order to investigate further the role of D-3 receptors in hypothermia and hypolocomotion, we tested the effects of ip administration of three DA receptor agonists reported to be selective for the D-3 receptor subtype (7-OH-DPAT, quinelorane and PD 128907) on core temperature and spontaneous locomotor activity in homozygous (D-3(-/-)), heterozygous (D-3(+/-))mutant and wild-type (D-3(+/+)) mice. Quinelorane (0.003-0.3 mg/kg), PD 128907 (1-10 mg/kg) and 7-OH-DPAT (0.1-3 mg,kg) induced hypothermia and decreased locomotion to a similar extent in the three genotypes. Additionally, the putatively selective DA D-3 receptor antagonist PNU 99194A (3-20 mg/kg ip) increased locomotor activity in habituated mice and reversed the hypothermia induced by 30 mu g/kg of quinelorane, with no apparent difference between D-3(-/-), D-3(+/-) and D-3(+/+) genotypes. The spontaneous level of locomotor activity of mutants (D-3(-/-) or D-3(+/-)) was found to be tither at, below, or above that of controls, with no consistent trend between different batches of mice. These results show that the presence of DA D-3 receptors is not necessary for the expression of these effects induced by the three agonists or the antagonist supposedly selective for the D-3 receptor subtype. This raises the question of the involvement of the D-3 receptor in these behavioural effects and the issue of the in vivo selectivity of these four compounds for the D-3 receptor subtype. Alternatively, possible adaptive mechanisms taking place in D-3(-/-) mice might have compensated for the absence of DA D-3 receptors. (C) 1999 Elsevier Science Ltd. All rights reserved.