THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS CAPTOPRIL AND ENALAPRIL INHIBIT APOMORPHINE-INDUCED ORAL STEREOTYPY IN THE RAT

The possible functional interaction between angiotensin and dopamine m echanisms in the rat was investigated by examining the effects of the angiotensin converting enzyme inhibitors captopril and enalapril on ap omorphine-induced stereotypy. Apomorphine-induced behaviour was observ ed, and recorded using a keypad linked to a microcomputer. in agreemen t with previous findings, low doses of apomorphine induced a syndrome of vacuous mouth movements, penile grooming, yawning and immobility wh ereas at higher doses the yawning syndrome disappeared to be replaced with sniffing, licking and gnawing. Two antagonism studies were carrie d out. In the first the effects of captopril on apomorphine-induced be haviour were compared with those of the classical neuroleptic haloperi dol, and in the second dose-response curves for the effects of captopr il and enalapril on apomorphine-induced behaviour were determined. Cap topril had no effect on the apomorphine-induced yawning syndrome where as this was blocked by haloperidol. In contrast, both captopril and ha loperidol blocked oral stereotypy (licking and gnawing) induced by apo morphine but had no effect on sniffing induced by the dopamine agonist . Selective blockade of apomorphine-induced oral stereotypy by angiote nsin converting enzyme inhibition was confirmed in the second study in which both captopril and enalapril were observed to antagonize apomor phine-induced gnawing. The inhibition of apomorphine-induced gnawing b y enalapril correlated with inhibition of brain angiotensin converting enzyme, but not lung angiotensin converting enzyme, by the drug as as sessed by ex vivo penetration studies. These data suggest that angiote nsin converting enzyme inhibition modulates the expression of apomorph ine-induced oral stereotypy, a response that is thought to be mediated by postsynaptic dopamine receptors. In contrast, the yawning syndrome induced by low doses of apomorphine which is thought to be due to sel ective stimulation of dopamine autoreceptors is unaffected by the angi otensin converting enzyme inhibitors. Thus the pharmacological interac tion between inhibition of brain angiotensin converting enzyme and blo ckade of apomorphine-induced oral stereotypy probably occurs at postsy naptic dopamine receptors or at downstream sites innervated by striata l neurones (e.g., substantia nigra or superior colliculus).