The role of catecholamines in desmopressin induced locomotor stimulation

Central and peripheral administration of DDAVP increase locomotor activity in rats in doses that alter brain dopamine neurochemistry. In order to deli neate the role of catecholamines in this behavioural effect of DDAVP, the e ffects of different catecholamine manipulating agents on DDAVP-induced loco motor stimulation were studied in rats. The catecholamine depleting agent r eserpine (5 mg/kg), administered alone or together with the catecholamine s ynthesis inhibitor alpha-methyltyrosine (250 mg/kg), completely prevented t he locomotor stimulatory effect of DDAVP. The dopamine D1 receptor antagoni st Sch-23390 (0.01 and 0.03 mg/kg) significantly antagonized the DDAVP-indu ced locomotor stimulation when administered in the higher dose, that also p roduced a significant reduction of locomotor activity per se, whereas the d opamine D2 receptor antagonist raclopride (0.08 and 0.16 mg/kg) had no sign ificant effect. The two dopamine blockers administered together produced a significant, dose-dependent reduction of DDAVP-induced locomotor stimulatio n, while controls were not significantly affected. Also the a-adrenoceptor antagonist phenoxybenzamine decreased the DDAVP-induced locomotor stimulati on in a dose (20 mg/kg) that did not influence locomotor activity in contro ls, and, finally, administration of Sch-23390, raclopride and phenoxybenzam ine antagonised the DDAVP-induced effect in a dose combination that failed to influence locomotor activity per se. In vivo microdialysis experiments i n awake, fr eely moving rats indicated that DDAVP increases dopamine overfl ow in the nucleus accumbens, a brain area of importance for initiation of l ocomotor activity, by approximately 25%. as compared to baseline levels. Ta ken together, these results indicate that the central stimulatory action of DDAVP involves granula-mediated dopamine release and subsequent activation of dopamine D1 and D2 receptors, and that a-adrenoceptors possibly also ar e involved.