(plus)minus UH 232, A partial agonist of the D3 dopamine receptors, attenuates cognitive effects of angiotensin IV and des-Phe6-angiotensin IV in the rats
We have recently found that the 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 effects 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 were examined. Male Wistar rats weighing 180–200 g were used. Both peptides given at the dose of 1 nmol facilitated recall of a passive avoidance (PA) behaviour, improved object recognition (OR), and increased apomorphineinduced stereotype behaviour. In the auxiliary tests performed to control for the unspecifi c infl uence of motor (open fi eld, OF) and emotional (“plus” maze, PM) effects of our treatments on the results of memory tests they had either no (OF) or negligible (PM) effects. Intraperitoneal pre-treatment of the animals with an ineffective on its own dose (1 mg/kg) of (+)-UH 232 abolished or markedly diminished effects of both peptides on PA and OR but did not infl uence enhancement of stereotypy caused by the peptides. These results indicate that the functional presynaptic DA D3 receptors are necessary for the pro-cognitive effects of Ang IV to occur.