Opiate
influences on drug-induced yawning in the
rat
Berendsen HHG , Gower AJ
Department of CNS
Pharmacology, Organon, Oss, The
Netherlands
Yawning can be elicited in laboratory
animals by various pharmacological agents
including apomorphine and physostigmine (Yamada
and Furukawa, 1980; Holmgren et al, 1980). The
response has been shown to be influenced by
androgens: castration will reduce drug-induced
yawning and pretreatment with testosterone will
restore it (Berendsen and Nickolson, 1980;
Holmgren et al, 1980). Since several studies,
e.g. Cicero et al. (1980), indicate an
interaction between androgens and opiates, we
tested whether an opiate link was involved in
the effect of testosterone on yawning.
All experiments were carried out between
8.30-12.30, using naive male Wistar rats
weighing 250-350 g. The effects of naloxone HCl,
morphine HCl, haloperidol and atropine SO4,
injected subcutaneously (s.c.) 20 min. before
testing, were determined on apomorphine HCl (40
and 80 µg/kg s.c.) or physostigmine
salicylate (100 pg/kg s.c.) induced yawning in
normal animals. Yawning responses were observed
in perspex observation cages (7.5 x 18 x 30 cm)
as described previously (Berendsen and
Nickolson, 1980) over a 20 min. period starting
immediately after apomorphine or 10 min. after
physostigmine. The effects of single doses of
naloxone, morphine, haloperidol and atropine
were also determined on the dihydrotestosterone
propionate-(DHTP) mediated increases in
apomorphine-induced yawning in chronically
castrated (at least 6 weeks) rats. DHTP, 125
µg/rat/day or arachis oil was injected s.c.
once daily for 3 consecutive days. 24 h. later
test drugs were injected s.c. 20 min. prior to
apomorphine (80 µg/kg) and yawning scored
as stated above.
Naloxone (1-10 mg/kg) partially antagonised
apomorphine or physostigmine-induced yawning. In
castrated rats, naloxone, 10 mg/kg inhibited the
DHTP mediated increases but had no effect on the
low level residual apomorphine yawning. In
normal rats, 0.32 and 1 mg/kg morphine had no
effect on apomorphine yawning but 3.2 mg/kg
caused marked inhibition; morphine (0.32-3.2
mg/kg) produced dose related inhibition of
physostigmine yawning. In castrated rats,
morphine, 1 mg/kg, inhibited the residual
apomorphine response but had no significant
effect on the DHTP-mediated increases.
Haloperidol (0.01-0.1 mg/kg) reduced apomorphine
yawning in normal rats. Haloperidol 0.01 mg/kg
significantly increased physostigmine yawning
but higher doses, 0.03 and 0.1 mg/kg had no
significant effect. Atropine reduced both
apomorphine and physostigmine yawning. In
castrated rats, haloperidol 0.1 mg/kg and
atropine 10 mg/kg inhibited both residual
apomorphine yawning and the DHTP-mediated
increases.
The finding that naloxone could not
completely block yawning in normal rats, but
blocked the DHTP effects suggests that this drug
inhibits drug-induced yawning by antagonising
the androgenic influences. However, in these
experiments, there was no evidence that morphine
treatment will enhance yawning. The blocking by
haloperidol and atropine of yawning in normal
rats and in castrated rats treated with DHTP or
arachis oil, supports the hypothesis that DHTP
acts as a permissive agent on yawning (Berendsen
and Nickolson, 1980). The effects of these drugs
also confirm previous findings (Yamada and
Furukawa, 1980) of an interaction between
dopaminergic and cholinergic effects on
yawning.
Berendsen, H.H.G. and Nickolson, V.J.
(1980). Behav. and Neural. Biol. 33,
123-128
Cicero, T.J. et al. (1980). Brain Res. 202,
151-164
Holmgren, B. et al. (1980). Acta Neurobiol.
Exp. 40, 515-519
Yamada, K. and Furukawa, T. (1980).
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HG, Gower AJ Opiate influences on
drug-induced yawning in the rat Behav Neural
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in drug-induced yawning and penile erections in
the rats Neuroendocrinology 1986; 42;
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-Berendsen
H et al Involvement of 5-HT1c-receptors in
drug-induced penile erections in rats
Psychopharmacology 1990; 101; 57-61
-Gower
AJ Effects of acetylcholine agonists and
antagonists on yawning and analgesia in the rat
Europ J Pharmacology 1987; 139; 79-89