Behavioral
studies on central dopaminergic
neurons.
especially
jumping, stretching, body shaking
and
yawning behavior
Yamada K, Furukawa T
Department of pharmacology,
School of Medicine, Fukuoka, Japan
Behavioral studies were performed in an
attempt to elucidate the involvement of
dopaminergic neurons in Jumping and sretching in
mice and body shaking and yawning in rats.
Alpha-naphthoxyacetic acid (a-NOAA) elicited
dose-dependent jumping and stretching behavior
at doses ranging from 250 to 700 mg/kg in mice
and vomiting at a dose of 550 mg/kg in pigeons.
Beta-NOAA also produced jumping behavior, but
the action was weaker than a-NOAA.
The (a-NOAA-induced jumping behavior was
only inhibited to a certain degree by
disulfiram, tranycypromine, haloperidol,
scopolamine, bicuculline, diazepam or lithium,
but was markedly inhibited by a dopaminergic
agonist, apomorphine, this inhibitory effect
being significantly antagonized by a
dopaminergic antagonist, haloperidol.
Apomorphine (2 mg/kg, i.p.) produced itself
neither stretching in mice nor vomiting in
pigeons though it induced marked feeding
(pecking) in pigeons. However protoveratrine-A
(0.1 mg/kg, /.p.), a veratrum alkaloid, also
induced stretching in mice and vomiting in
pigeons.
The characteristic stretching elicited by
a-NOAA or protoveratrine-A was not significantly
affected by scopolamine, aminooxyacetic acid and
y-butyrolactone, but was markedly inhibited by
apomorphine, this inhibitory effect being
antagonized without significance by haloperidol
which did not itself augment the stretching.
Moreover, intraperitoneal injections of a-NOAA
at doses of 550 and 700 mg/kg in mice exhibited
a significant increase of brain dopamine levels.
These results indicate that the jumping and
stretching behavior elicited by a-NOAA may be
due to the inhibition of dopaminergic neuronal
activity.
Low doses (0.25 mg/kg, i.p.) of apomorphine,
which preferentially activate presynaptic
dopamine autoreccptors, elicited yawning in
rats. Whereas apomorphine, at a high dose of 2
mg/kg, produces stereotypy which has been
thought to be mediated by stimulation of
postsynaptic dopamine receptors. The yawning and
stereotypy did not occur simultaneously in the
rat. The apomorphine-induced yawning was
completely inhibited by pretreatment with
fluphenazine or scopolamine, but markedly
increased by reserpine though it was not
affected by methylscopolamine.
Piribedil also elicited yawning at a low
dose of 5 mg/kg (i.p.) and stereotypy at a high
dose of 80 mg/kg. The yawning produced by
piribedil was significantly blocked by fluphena
zine, scopolamine and methysergide. Both
physostigmine (0.2 mg/kg, i.p.), an indirect
acetylcholine agonist, and pilocarpine (4 mg/kg,
LP.), a direct acetylcholine agonist, also
induced yawning, which was abolished by
scopolamine and increased by reserpine.
Fluphenazine did not affect the
pilocarpine-induced yawning but increased the
physostigmine-induced yawning. In addition, the
physostigmine-induced yawning was mark edly
inhibited by apomorphine but not by a selective
antiserotonergic drug, methysergide, whereas the
pilocarpine-induced yawning was not affected by
either apomorphine or methysergide.
Alpha-melanocyte-stimulating hormone, (alpha
MSH, 10 µg/i. vent.) induced yawning an
stretching but it also produced body shaking.
Yawning synchronized with stretching in almost
all cases. Yawning and stretching were gradually
increased after injection and was marked at
90-100 min and 60-70 mm, respectively, while
body shaking began within 5 min and was marked
at 10-20 min after injection. Body shaking was
also produced by the combined treatment with
5-hydroxytryptophan (150 mg/kg, s.c.) and Ro
4-4602 (50 mg/kg, i.p.) accompanied scarcely by
yawning and stretching.
The a-MSH-induced yawning and stretching
were blocked by scopolamine, apomorphine
fluphenazine and methysergide, while body shak
ing was not blocked by scopolamine but decreased
by apomorphine, fluphenazine and methysergide.
The results indicate that apomorphine and
piribedil elicit yawning by stimulating
presynaptic dopamine receptors and the yawning
concomitantly involves serotonergic activation,
dopaminergic inhibition and cholinergic
activation, and that the jumping and stretching
behavior seem to be due to dopaminergic
inhibition and the body shaking due to
serotonergic activation.
-Fugikawa
M; Yamada K; Nagashima M; Furukawa T
Involvement of beta-adrenoreceptors in
regulation of the yawning induced by
neuropeptides; oxytocin and alpha-melanocytes
stimuling hormone in rats. Pharmacol Biochem
Behav 1995; 50; 339-343
-Furukawa
T Yawning behavior for preclinical drug
evaluation Meth Find Exp Clin Phamacol 1996; 18;
2; 141-155
-Kimura H;
Yamada K; Nagashima M; Matsumoto S Role of
adrenergic neuronal activity in the yawning
induced by tacrine and NIK-247 in rats.Pharmacol
Biochem Behav 1992; 43; 4; 985-91
-Kimura
H; Yamada K; Nagashima M; Furukawa T
Involvement of catecholamine receptor activities
in modulating the incidence of yawning in
rats.Pharmacol Biochem Behav 1996; 53(; 4;
1017-21
Ogura
H, Kosasa T, Kuriya Y, Yamanishi Y Central
and peripheral activity of cholinesterase
inhibitors as revealed by yawning and
fasciculation in rats. Eur J Pharmacol. 2001;
415; 2-3; 157-64
-Serra
G , Collu M and Gessa GL Yawning is elicited
by D2 dopamine agonists but is blocked by D1
antagonist Psychopharmacology 1987; 91;
330-337
-Serra G,
Gessa GL Hypophysectomy prevents yawning and
penile erection but not hypomotility induced by
apomorphine Pharmacology Biochemistry &
Behavior 1983; 19; 917-919
-Serra G
et al Cycloheximide prevents apomporphine
induced yawning, penile erection and genital
grooming in rats European Journal of
Pharmacology1983; 86; 279-282
-Kostrzewa RM
and R Brus Is dopamine-agonist induced
yawning behavior a D3 mediated event? Life Sci
1991; 48; 26; 129
-Ushijima I,
Mizuki Y, Yamada M Multifocal sites of
action involved in dopaminergic-cholinergic
neuronal interactions in yawning
Psychopharmacology (Berl) 1988; 95; 34-7
-Ushijima
I et al, Muscarinic and nicotinic effects on
yawning and tongue protruding in the rat
Pharmacol Biochem Behavior 1984; 21;
297-300
-Ushijima
et al modification of apomorphine,
physiostigmine and pilocarpine induced yawning
after long term treatment with neuroleptic or
cholinergic agents Arch Int Pharmacodyn 1984;
271; 180-188
-Ushijima
I et al Characteristics of yawning behavior
induced by apomorphine, physostigmine and
pilocarpine Arch Int Pharmacodyn 1985; 273;
196-201
-Ushijima,
I., Y. Mizuki, et al. Behavioral effects of
dilazep on cholinergic, dopaminergic, and
purinergic systems in the rat. Pharmacol Biochem
Behav 1992;43(3): 673-676.
-Yamada K,
Furukawa T Direct evidence for involvement
of dopaminergic inhibition and cholinergic
activation in yawning Psychopharmacology 1980;
67; 39-43
-Yamada K,
Furukawa T The yawning elicited by
alpha-melanocyte-stimulating hormone involves
serotonergic -dopaminergic - cholinergic neuron
link in rats Naunyn-Schmiedeberg's Arch
Pharmacol 1981; 316; 155 -160
-Yamada K et
al Involvement of septal and striatal
dopamine D2 receptors in yawning behavior in
rats Psychopharmacology 1986; 90; 9-13
-Yamada K
et al Possible involvement of differing
classes of dopamine d2 receptors in yawning and
stereotypy in rats Psychopharmacology 1990; 100;
141-144
-Yamada K,
Furukawa T Behavioral studies on central
dopaminergic neurons. especially jumping,
stretching, body shaking and yawning behavior J
PharmacoBio dynamics 1980; 3; S16-S18