[Age-related modification of dopaminergic-cholinergic neuronal interaction in rats].
A behavioral study was performed in an attempt to understand the effect of age (rats aged 2, 6, 12, 18, or 24 months) on the dopaminergic-cholinergic neuronal mechanism involved in yawning and stereotyped behaviors induced by dopaminergic and cholinergic drugs. Intraperitoneal (ip) injection of a low dose of apomorphine (0.1 mg/kg), which preferentially activates presynaptic dopamine autoreceptors, produced a lower frequency of yawning responses in 12- and 24-month-old rats than in 2-month-old rats. A high dose of apomorphine (0.5 mg/kg) which stimulates both pre- and post-synaptic dopamine receptors produced the most pronounced stereotyped behavior in 12-month-old rats. The peak times for apomorphine-induced stereotypy shifted to the right between 2- and 12- and 24-month-old rats, and the duration of the stereotypy also increased in 12- and 24-month-old rats as compared with 2-month-old rats. It is suggested that decreased function of the presynaptic dopamine receptors might contribute to the increased stereotypy induced by apomorphine with increasing age in the rat. Yawning responses induced by pilocarpine (4 mg/kg) were reduced in 6- to 24-month-old rats whereas those by physostigmine (0.2 mg/kg) were not affected in rats of any age. These results suggest that differential pathways are involved in dopaminergic-cholinergic neuronal interaction, and that with increasing age, cholinergic neurons activated by cholinesterase inhibition (endogenous acetylcholine) were not affected but those by a direct acetylcholine agonist (muscarinic M-1 receptor agonist) were diminished.
Kishimoto
O
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Department of Neuropsychiatry, Yamaguchi University School of Medicine, Japan.
D000375:Aging / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D015000:Yawning / Q000187:drug effects*
D008781:Methyltyrosines; D010862:Pilocarpine; C022260:alpha-methyltyrosine methyl ester; D012110:Reserpine; D010830:Physostigmine; D001058:Apomorphine