captopril
and enalapril inhibit
apomorphine-induced
oral
stereotypy in the rat
Banks RJ, Mozley L, Dourish CT.
Department of Psychology,
University of Sheffield, U.K.
The possible functional interaction between
angiotensin and dopamine mechanisms in the rat
was investigated by examining the effects of the
angiotensin converting enzyme inhibitors
captopril and enalapril on apomorphine-induced
stereotypy. Apomorphine-induced behaviour was
observed, and recorded using a keypad linked to
a microcomputer. In agreement with previous
findings, low doses of apomorphine induced a
syndrome of vacuous mouth movements, penile
grooming, yawning and immobility whereas at
higher doses the yawning syndrome disappeared to
be replaced with sniffing, licking and
gnawing.
Two antagonism studies were carried out. In
the first the effects of captopril on
apomorphine-induced behaviour were compared with
those of the classical neuroleptic haloperidol,
and in the second dose-response curves for the
effects of captopril and enalapril on
apomorphine-induced behaviour were determined.
Captopril had no effect on the
apomorphine-induced yawning syndrome whereas
this was blocked by haloperidol. In contrast,
both captopril and haloperidol blocked oral
stereotypy (licking and gnawing) induced by
apomorphine but had no effect on sniffing
induced by the dopamine agonist. Selective
blockade of apomorphine-induced oral stereotypy
by angiotensin converting enzyme inhibition was
confirmed in the second study in which both
captopril and enalapril were observed to
antagonize apomorphine-induced gnawing.
The inhibition of apomorphine-induced
gnawing by enalapril correlated with inhibition
of brain angiotensin converting enzyme, but not
lung angiotensin converting enzyme, by the drug
as assessed by ex vivo penetration studies.
These data suggest that angiotensin
converting enzyme inhibition modulates the
expression of apomorphine-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 selective stimulation of dopamine
autoreceptors is unaffected by the angiotensin
converting enzyme inhibitors. Thus the
pharmacological interaction between inhibition
of brain angiotensin converting enzyme and
blockade of apomorphine-induced oral stereotypy
probably occurs at postsynaptic dopamine
receptors or at downstream sites innervated by
striatal neurones (e.g., substantia nigraor
superior colliculus).
-Banks RJ,
Mozley L, Dourish CT. The angiotensin
converting enzyme inhibitors captopril and
enalapril inhibit apomorphine-induced oral
stereotypy in the rat. Neuroscience.
1994;58(4):799-805
-Stoessl
AJ, Dourish CT, Iversen SD
Apomorphine-induced yawning in rats is abolished
by bilateral 6-hydroxydopamine lesions of the
substantia nigra Psychopharmacol; 1987; 93;
336-342
-Stoessl
AJ Effects of ageing on the behavioural
responses to dopamine agonists: decreased
yawning and locomotion, but increased stereotypy
Brain Research 1989; 495; 20-30
-Stoessl AJ,
Dourish CT, Iversen SD The NK-3 tachykinin
agonist senktide elicits yawning and chewing
mouth movements following subcutaneous
administration in the rat. Evidence for
cholinergic mediation. Psychopharmacology
(Berl). 1988; 95; 4; 502-506
-Cooper SJ;
Dourish CT Neural basis of drug induced
yawning in neurobiology of stereotyped behaviour
Oxford ed 1990
-Cooper SJ,
Rusk IN, Barber DJ. Yawning Induced by the
Selective Dopamine D2 Agonist N-0437 is Blocked
by the Selective Doparnine Autoreceptor
Antagonist (+)-UH 232. Physiol Behav.
1989;45:1263-1266
-Dourish
CT, SJ Cooper Yawning elicited by sytemic
and intrastriatal injection of piribedil and
apomorphine in the rat Pyschopharmacology 1985;
86; 175-181
-Dourish CT,
PH Hutson Bilateral lesions of the striatum
induced with 6-hydroxydopamine abolish
apomorphine-induced yawning in rats
Neuropharmacology 1985; 24; 11; 1051-1055
-Collins G, JM
Witkin et al Dopamine agonist-induced
yawning in rats: a dopamine d3 receptor mediated
behavior J Pharmacol Exp Ther 2005
