[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.

[Effects of bifemelane on central dopaminergic and cholinergic systems in rats].

The study served to examine the effects of bifemelane on central dopaminergic-cholinergic neuronal mechanisms in rats. Bifemelane (5-20 mg/kg) evoked yawning responses, the frequency being low. Bifemelane (10 mg/kg) as well as bromocriptine (2.5 mg/kg) potentiated physostigmine (0.2 mg/kg)-, bromocriptine (2.5 mg/kg)- or apomorphine (0.1 and 0.5 mg/kg)-induced yawning but completely inhibited pilocarpine-induced yawning. Pretreatment with sulpiride (20 mg/kg) and a low dose of haloperidol (0.02 mg/kg) reversed the stimulatory effect of bifemelane on physostigmine-induced yawning and the inhibitory effect of the drug on pilocarpine-induced yawning, whereas atropine (5 mg/kg) diminished these yawning responses. SK&38393 (2.0 mg/kg), a dopamine D-1 receptor agonist, markedly potentiated bifemelane- and bromocriptine-induced yawning but inhibited physostigmine-induced yawning, and did not affect pilocarpine-induced yawning. The increased yawning responses were blocked by atropine and a low dose of haloperidol. Bifemelane (10 mg/kg) and bromocriptine (2.5 mg/kg) tended to increase apomorphine (5 mg/kg)-induced oral stereotypy, such as licking and biting, but the increase was not significant. These results suggest that the effects of bifemelane on central dopaminergic and cholinergic neurons may be similar to those of bromocriptine.

Effects of age on behavioral responses to dopamine agonists in the rat.

This study served to examine the differential effects of age (rats aged 2 or 12 months) on behavioral responses induced by bromocriptine and apomorphine. Intraperitoneal (i.p.) injection of bromocriptine or apomorphine produced a lower frequency of yawning responses, in 12-month-old rats than in 2-month-old rats. Apomorphine produced a more pronounced stereotyped behavior in 12-month-old rats than in 2-month-old rats. Apomorphine, at 0.1 mg/kg administered after bromocriptine (1.0-20 mg/kg) potentiated yawning behavior. The frequency of yawning in 2-month-old rats was pronounced at 2.5 mg/kg of bromocriptine but only at 5 mg/kg 12-month-old rats. Apomorphine (0.1 mg/kg) did not produce perioral behavior in 2-month-old rats but did in 12-month-old rats. The apomorphine (1.0 mg/kg)-induced stereotypy was stimulated dose dependently by bromocriptine in 2-month-old-rats but not in 12-month-old rats. Bromocriptine did not produce this behavior when administered alone. Pretreatment of 2-month-old rats with reserpine, a catecholamine depletor, plus alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, inhibited the yawning induced by bromocriptine but potentiated that induced by apomorphine. Such treatment did not significantly alter either bromocriptine or apomorphine-induced yawning responses in 12-month-old rats. The apomorphine-induced stereotypy in 2-month-old rats was markedly potentiated by catecholamine depletion but was not affected in 12-month-old rats. These results suggest that the increasing effect on stereotypy and decreasing effects on yawning in the 12-month-old rats seem to result in an alteration of potency and of the ratio of D-2 versus D-1 receptor activity.