Multifocal
sites of action involved in
dopaminergic-cholinergic neuronal interactions
in yawning
Itsuko Ushijima, Yasushi Mizuki, and Michio
Yamada
Department of
Neuropsychiatry, Yamaguchi University, School of
Medicine, Ube Japan
Bromocriptine (BRQ, a dopamine
D-2 receptor agonist, physostigmine, an
anticholinesterase agent and pilocarpine,
a muscarinic cholinergic receptor agonist,
produced yawning in rats, with the most
effective doses being 2.5 mg/kg, 0.2 mg/kg and 4
mg/kg, respectively.
BRC-induced yawning was inhibited by high
doses of SK&F38393 (5 and 10 mg/kg), a
selective D-1 receptor agonist. BRC or
SK&F38393 alone did not induced stereotyped
behaviors. However, when BRC was administered
after SK&F38393 (5.0 and 10 mg/kg),
stereotyped behaviors occurred; i.e., mainly
sniffing at 2.5 and 5.0 mg/kg BRC, and mainly
licking and biting 10 and 20 mg/kg BRC.
A high dose of apomorphine (4 mg/kg IP)
completely inhibited physostigmine-induced
yawning (physostigmine yawning) but did not
affect pilocarpine-induced yawning (pilocarpine
yawning). BRC (2.5-20 mg/kg) increased
physostigmine yawning in an additive
fashion.
Pilocarpine yawning was completely blocked by
either low or high doses of BRC. The inhibitory
effect of BRC on pilocarpine yawning was
reversed by sulpiride (20 mg/kg).
oc-Methyl-p-tyrosine (aMPT; 100 and 200 mg/kg)
did not affect physostigmine yawning but
diminished pilocarpine yawning. Furthermore,
physostigmine (0.2 mg/kg) inhibited apomorphine
(4.0 rng/ kg)-induced hyperlocomotion and
sniffing but not licking and biting, whereas
pilocarpine (4.0 mg/kg) had the opposite
effect.
These results suggest that activation of
postsynaptic dopamine receptors (primarily D-1
receptors) may inhibit cholinergic neurons
activated by cholinesterase inhibition, i.e.,
endogenous acetylcholine, and that the
postsynaptic sensitivity of cholinergic neurons
to a direct acetylcholine agonist (muscarinic
M-1 receptor agonist) may be reduced by
stimulation of presynaptic dopamine receptors
(D-2 receptor) and/or inhibition of dopamine
synthesis.
Bromocriptine (BRC), a selective dopamine D-2
receptor agonist, has been reported to evoke
yawning in rats (Protais et al. 1983).
Similarly, cholinomimetic drugs and low doses of
apomorphine, a non-selective dopamine receptor
agonist. also induce yawning (Urba-Holmgren et
al. 1977; Yamada and Furjikawa 1980, 1981).
Yawning induced by apomorphine, physostigmine or
pilocarpine is inhibited by scopolamine, a
muscarinic receptor blocking agent, but not by
methylscopolamine, a peripheral anticholinergic
agent or by mecamylamine, a nicotinic receptor
blocking agent.
This suggests involvement of central
muscarinic receptors (UrbaHolmgren et al. 1977;
Yamada and Furukawa 1980. 1981) but not central
nicotinic receptors (Ushijima et al. 1985) in
mediating yawning behavior. In addition, since
low doses of haloperidol inhibit
apomorphine-induced yawning, it is possible that
this behavior may be mediated by cholinergie
activation secondary to the inhibition of
dopamine transmission (Yamada and Furukawa 1980:
Ushijima et al. 1985). Furthermore, there is
evidence suggesting that acetylcholine release
is controlled by the dopamine D-2 receptor
(Closse et al. 1985). Physostigmine-induced
yawning is potentiated by fluphenazine, a
long-acting neuroleptic, but is inhibited by
higher doses of apomorphine, whereas
pilocarpine-induced yawning is not affected by
either drug, suggesting that the sensitivity of
cholinergie neurons to a cholinesterase
inhibitor, physostigmine, but not to a direct
acetylcholine agonist, pilocarpine, may be
altered in the dopaminergie-cholinergic neuronal
interactions. However, reserpine, a
catecholamine depletor, activates apomorphine-,
physostigmine- and pilocarpine-induced yawning
(Yamada and Furukawa 1980). The present studies
were designed to clarify
dopaminergic-cholinergic mechanisms involved in
mediating drug-induced yawning responses.
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