The role of dopamine in the facilitatory effect of angiotensin II on impaired learning in rats chronically treated with ethanol.

Abstract

Rats with impaired active avoidance induced by chronic (9 weeks) administration of ethanol were studied. Angiotensin II (ANG II) administered (ICV, 2.0 micrograms) 12 h after the withdrawal of the alcohol not only neutralized the toxic effect of ethanol but also improved learning. When administered on the 5th day after ethanol withdrawal, the effect of ANG II was weaker. Tests of stereotypy and catalepsy were used to study the possible role of the dopaminergic system in this action of ANG II. It was shown that both chronic alcohol treatment and ANG II alone increased apomorphine (1 mg/kg) and amphetamine (7.5 mg/kg) stereotypy but the effects of ANG II were greater. ANG II did not change the stereotypy induced by amphetamine but increased the stereotypy induced by apomorphine in the group of animals chronically treated with alcohol. Haloperidol-induced catalepsy was reduced in these rats. ANG II alone intensified catalepsy and eliminated the effect of ethanol. Both ANG II and alcohol increased striatal dopamine (DA) concentration. This effect of ANG II was significantly greater in the animals chronically treated with alcohol. The above changes were not observed after the DA level had been reduced by alpha-methyl-p-tyrosine (250 mg/kg), nor were changes observed in the striatal DOPAC. The results suggest involvement of the central dopaminergic system in the effect of ANG II on the ethanol-induced impairment of acquisition of active avoidance but, however, the results of the biochemical determinations of DA turnover do not provide an explanation of these changes.