Bilateral
lesions of the striatum induced with
6-hydroxydopamine abolish apomorphine-induced
yawning in rats
CT Dourish, PH Hutson
Department of
Neurochemistry, Institute of Neurology, The
National Hospital, London
Considerable interest has developed in a
syndrome of yawning and sexual arousal which is
produced by small doses of dopamine agonists in
rats. The yawning syndrome is thought to be the
consequence of an inhibition of dopaminergic
transmission in the brain mediated by the
stimulation of dopamine autoreceptors.
Thus, doses of dopamine agonists which
produce yawning, after systemic injection, are
within the range thought to activate
autoreceptors, but smaller than doses required
to, produce signs of stimulation of postsynaptic
dopamine receptors, such as hyperactivity and
stereotypy. In addition, novel drugs, which are
claimed to be selective dopamine autoreceptor
agonists produce yawning in rats. Yawning
induced by dopamine agonists appears to be
centrally mediated since the response is
elicited by microinjection of piribedil and
apomorphine into dopamine-containing terminal
regions of the forebrain. Furthermore, yawning
induced by apomorphine is abolished by the
centrally-acting dopamine antagonist
haloperidol, but unaffected by the peripheral
dopamine antagonist domperidone.
In the present study, evidence is provided
that apomorphine-induced yawning and chewing is
depenilent on the integrity of the dopaminergic
innervation of the striatum, since the response
to, a small dose of apomorphine, given
systemically, was abolished by bilateral lesions
of the striatum induced with 6-hydroxydopamine
(6-OHDA). [...]
DISCUSSION
The present data confirm many previous
findings that a small dose of apomorphine
produces a syndrome of yawning and sexual
arousal in male rats. Most previous authors have
suggested that yawning induced by dopamine
agonists is mediated by presynaptic dopamine
autoreceptors.
In the present study, the yawning syndrome
(i.e. yawning, chewing, penile grooming) was
abolished by a 58% depletion of striatal
dopamine, produced by bilateral lesions of the
striatum, induced by 6-OHDA. These data are
consistent with the mediation of yawning by
presynaptic dopamine receptors since it is well
established that postsynaptic dopamine receptors
become supersensitive to direct dopamine
agonists after dopaminergic denervation. For
example, rats with lesions of the striatum and
nucleus accumbens induced with 6-OHDA show
enhanced locomotor stimulation and stereotypy
(ie. sniffing, head movements, gnawing) in
response to apomorphine, compared to intact
animals.
Indeed, in the present study, there was
limited evidence for the development of
supersensitivity of postsynaptic dopamine
receptors since a number of rats lesioned with
6-OHDA were observed to exhibit increased
sniffing in response to 0.1 mg/kg of
apomorphine. In contrast, increased sniffing was
never observed in intact animals or sham
controls after this drug dose (N.B. 0.2-0.5
mg/kg apomorphine is reported to be the
threshold dose to elicit sniffing in rats.
However, it should be noted that the possibility
of mediation of yawning by postsynaptic dopamine
receptors cannot be completely ruled out at
present. Apomorphine-induced yawning exhibits a
bell-shaped dose-response curve and yawning is
generally produced by 0.025-0.2 mg/kg of the
drug. In the present study only one dose of
apomorphine (0. 1 mg/kg) was tested and
therefore it is possible that the lesions
induced with 6-OHDA may have produced a shift to
the left in the dose-response curve which could
have caused the disappearance of yawning at the
dose of 0.1 mg/kg.
The data indicate that dopaminergic
innervation of the striatum plays an important
role in the mediation of yawning induced by
dopamine agonists. This is consistent with the
observation that microinjection of piribedil and
apomorphine into the striatum elicits an
identical syndrome of yawning, chewing and
sexual arousal.
Previous studies have reported that sexual
arousal (i.e. penile grooming, erection and
ejaculation) and occasional stretching are
associated with yawning induced by dopamine
agonists in male rats. However, only one
previous study has reported that chewing mouth
movements are associated with yawning. The
prescrit findings are in agreement with the
latter study and show that chewing generally
precedes and succeeds yawning induced by
systemie or intrastriatal injection of dopamine
agonists. Furthermore, the present study showed
that depletion of dopamine in the striatum
abolished not only yawning induced by
apomorphine but also sexual arousal and chewing.
Therefore, chewing jaw movements may be an
integral part of the yawning syndrome, induced
by dopamine agonists, in male rats.
-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
