(+)-UH 232, a partial agonist of the D₃ dopamine receptors, attenuates cognitive effects of angiotensin IV and des-Phe⁶-angiotensin IV in rats

Abstract 

We have recently found that postsynaptic D₃ dopamine (DA) receptors appear not to participate in the memory enhancing effects of the angiotensin AT₄ receptor agonists angiotensin IV (Ang IV) and des-Phe⁶-Ang IV. In this study we evaluated role of the presynaptic DA D3 receptors in these effects. For that purpose effect of (+)-UH 232, a selective D3 DA receptors partial agonist preferring presynaptic sites, on the pro-cognitive action of intracerebroventricularly (icv) injected Ang IV and des-Phe⁶-Ang IV was examined. Male Wistar rats weighing 180–200g were used. Both peptides given at the dose of 1nmol facilitated recall of a passive avoidance (PA) behaviour, improved object recognition (OR), and increased apomorphine-induced stereotype behaviour. In the auxiliary tests performed to control for the unspecific influence of motor (open field, OF) and emotional (‘plus’ maze, PM) effects of our treatments on the results of the memory tests they had either no (OF) or negligible (PM) effects. Intraperitoneal pre-treatment of the animals with an ineffective on its own dose (1mg/kg) of (+)-UH 232 abolished or markedly diminished effects of both peptides on PA and OR but did not influence enhancement of stereotypy caused by the peptides.

Keywords: Angiotensin IV, Des-Phe⁶-angiotensin IV, (+)-UH 232, Dopamine D₃ receptor, Stereotype behaviour, Memory, Rat