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Abstract: Bifeprunox and aripiprazole are two novel antipsychotics presenting partial agonistic activity for the D2 and D3 dopamine (DA) receptors. Using in vivo electrophysiological paradigms in anaesthetized rats, we have previously shown that both drugs independently inhibit the spontaneous firing and bursting activity of ventral tegmental area (VTA) dopaminergic neurons and partially reverse the suppressing effect of the full DA receptor agonist apomorphine. Moreover, we have also shown that the D2/3 receptor antagonist haloperidol prevents the inhibitory effects of these antipsychotics, confirming their partial D2-like agonistic activities [L. Dahan, H. Husum, O. Mnie-Filali, J. Arnt, P. Hertel, N. Haddjeri, Effects of bifeprunox and aripiprazole on rat serotonin and dopamine neuronal activity and anxiolytic behaviour, J. Psychopharmacol. (2009)]. In the present electrophysiological study, selective antagonists of D2 and D3 receptors were used to further characterize the inhibitory role of bifeprunox and aripiprazole on the D2 and D3 receptors in vivo. Administration of bifeprunox (250μg/kg, i.v.) or aripiprazole (300μg/kg, i.v.) reduced the firing activity of VTA DA neurons by 40–50%. The bursting activity was reduced by 95% and 77% by bifeprunox and aripiprazole, respectively. Systemic administration of the preferential D3 receptor antagonist GR218,231 (200μg/kg, i.v.) did not modify the inhibitory effect of bifeprunox or aripiprazole, either on the firing or on the bursting activity. On the other hand, the preferential D2 receptor antagonist L741,626 (500μg/kg, i.v.) completely blocked the inhibitory effect of both bifeprunox and aripiprazole on the VTA DA neuronal activity. The present study shows that bifeprunox and aripiprazole behave as partial D2, but not D3, receptor agonists in vivo, inhibiting the firing activity (preferentially the phasic activity) of VTA DA cells. [Copyright &y& Elsevier]

Abstract: The physiological function of 5-HT7 receptors is not yet fully determined. This study was designed to characterize the involvement of 5-HT7 receptor in rat body temperature regulation and in adrenocorticotropic hormone (ACTH) and corticosterone secretion. In the first part of our study, acute administration of SB-269970 (0.1–1mg/kg, i.p.), a potent and selective 5-HT7 receptors antagonist, dose-dependently prevented 5-HT1A/7 receptor agonist 8-OH-DPAT (0.1mg/kg, s.c.)-induced hypothermia and when the 5-HT1A receptor antagonist WAY-100,635 was co-injected with SB-269970, a reduction of the latter hypothermia was obtained in an additive manner. In contrast, 1mg/kg (i.p.) of SB-269970 failed to prevent 8-OH-DPAT (0.5mg/kg, s.c.)-induced increase of ACTH and corticosterone plasma levels. In conclusion, the present results unveil an additive effect of both 5-HT1A and 5-HT7 receptors in core body temperature regulation. [Copyright &y& Elsevier]