Desmopressin and vasopressin increase locomotor activity in the rat via a central mechanism: implications for nocturnal enuresis.

Abstract

Nocturnal enuresis is characterized by nocturnal urine volumes exceeding bladder capacity and by inability to wake up to the stimulus of a full bladder. Desmopressin (DDAVP) is believed to be efficient in treating nocturnal enuresis by reducing nocturnal urine production. However, clinical observations indicate an additional mode of action since the drug appears to modify sleep architecture, apparently improving the patient's ability to awaken to the stimulus of a full bladder. Because of this, a possible arousing effect of DDAVP was studied. The tentative ability of DDAVP and the endogenous hormone vasopressin (AVP) to produce locomotor stimulation in resting rats after both intracerebroventricular and subcutaneous administration was used as an animal model of arousal. In addition brain monoamine biochemistry was analyzed. The intracerebroventricular injection of AVP (0.1 and 1 microgram.) and the intracerebroventricular (0.1, 1, 10 and 100 microgram.) and subcutaneous (90 and 180 microgram.) injections of DDAVP were both associated with a significant increase in the locomotor activity of the animals compared with controls. The biochemical analysis of cerebral monoamines indicated that DDAVP lowers brain dopamine levels after both types of administration. These results suggest that DDAVP exerts a stimulatory effect in the CNS, which is also observed after peripheral administration. There are also indications for an increase in central dopamine turnover which could explain the registered increase in locomotor activity.