Injection Of Cholinergic Agents Research Articles

Involvement of dorsal hippocampal muscarinic cholinergic receptors on muscimol state-dependent memory of passive avoidance in mice

Aims In the present study, the effects of bilateral intra-dorsal hippocampal (intra-CA1) injections of cholinergic agents on muscimol state-dependent memory were examined in mice. Main methods A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Key findings Pre-training intra-CA1 administration of a GABA-A receptor agonist, muscimol (0.05 and 0.1 μg/mouse) dose dependently induced impairment of memory retention. Pre-test injection of muscimol (0.05 and 0.1 μg/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under pre-training muscimol (0.1 μg/mouse, intra-CA1) influence. Pre-test intra-CA1 injection of an acetylcholinesterase inhibitor, physostigmine (0.5 and 1 μg/mouse, intra-CA1) reversed the memory impairment induced by pre-training administration of muscimol (0.1 μg/mouse, intra-CA1). Moreover, pre-test administration of physostigmine (0.5 and 1 μg/mouse, intra-CA1) with an ineffective dose of muscimol (0.025 μg/mouse, intra-CA1) significantly restored the retrieval and induced muscimol state-dependent memory. Pre-test intra-CA1 administration of physostigmine (0.25, 0.5 and 1 μg/mouse) by itself cannot affect memory retention. Pre-test intra-CA1 injection of the muscarinic receptor antagonist, atropine (1 and 2 μg/mouse) 5 min before the administration of muscimol (0.1 μg/mouse, intra-CA1) dose dependently inhibited muscimol state-dependent memory. Pre-test intra-CA1 administration of atropine (0.5, 1 and 2 μg/mouse) by itself cannot affect memory retention. Significance The results suggest that muscarinic cholinergic mechanism of the CA1 may influence muscimol state-dependent memory.

The influence of central administration of dopaminergic and cholinergic agents on morphine-induced amnesia in morphine-sensitized mice

In the present study, effects of intracerebroventricular (i.c.v.) injections of dopaminergic and cholinergic agents on morphine-induced amnesia in morphine-sensitized mice were investigated by using a one-trial passive avoidance task. Amnesia induced by pre-training morphine was significantly reversed in morphine-sensitized mice, which had previously received once daily injections of morphine (20 and 30 mg/kg, s.c.) for 3 days. Three daily injections of SKF 38393 (1, 2 and 4 g/mouse, i.c.v.) or SCH 23390 (0.25, 0.5, 0.75 and 1 g/mouse, i.c.v.) before morphine, and during morphine-sensitization, decreased and increased the amnesia induced by pre-training morphine respectively. Three daily injections of quinpirole (0.3, 1 and 3 g/mouse, i.c.v.) or sulpiride (0.03, 0.1, 0.3 and 1 g/mouse, i.c.v.) before morphine, also decreased and increased the amnesia induced by pre-training morphine respectively. Morphine-sensitized mice received similar injections of cholinergic agents. Three daily injections of physostigmine (1, 3 and 5 g/mouse, i.c.v.) or atropine (1, 4 and 7 g/mouse, i.c.v.) before morphine, and during morphine-sensitization, decreased and increased the amnesia induced by pre-training morphine respectively. Three daily injections of nicotine (0.75, 1 and 2 g/mouse, i.c.v.) or mecamylamine (1, 3 and 6 g/mouse, i.c.v.) before morphine, also decreased and increased the amnesia induced by pre-training morphine respectively. The results suggest that morphine sensitization affects the impairment of memory formation and thus it is postulated that central dopaminergic and cholinergic systems may play an important role in this effect.

Plasma cyclic GMP: Response to cholinergic agents

S.c. injections of cholinergic agents, carbachol, methacholine and bethanechol, into fasted rats caused rapid increases in the plasma concentration of cyclic GMP, with a sharp peak at 5–10 min after the injection. Acetylcholine gave rise to a rapid accumulation of cyclic GMP in plasma only when administered together with physostigmine which produced only a slight, if any, potentiation of the action of the cholinesterase-resistant choline esters. Cyclic AMP also increased after these drugs, but only subsequently to the rise of cyclic GMP; the primary action of the cholinergic drugs appeared to be the increase in cyclic GMP. Atropine was effective not only in abolishing the increase in plasma cyclic GMP induced by cholinergic drugs but also in lowering the baseline level of cyclic GMP. It was concluded that the concentration of cyclic GMP could serve as a good parameter of cholinergic activity in rats.

Analysis of the tremor induced by injection of cholinergic agents into the caudate nucleus

Several cholinergic compounds (acetylcholine analogues, oxotremorine, and arecoline), all possessing muscarinic activity in the peripheral autonomic nervous system, evoked tremor after injection into the caudate nucleus of unanesthetized cats. Of the alkaloids and synthetic agents administered, carbachol was the most potent. Similar tremorogenic responses were not demonstrated after nicotine. Carbachol tremor was blocked by subsequent intracaudate injections of muscarinic antagonists, such as the belladonna alkaloids and their synthetic counterparts, but was not altered by other locally injected cholinergic antagonists, e.g. those which block the peripheral actions of nicotine. These results indicate that the cholinergic tremorogenic agents produce involuntary movements by a specific neuropharmacologic action on “muscarinic” receptors in the caudate. Tremor also develops after intracaudate physostigmine, an anticholinesterase, which permits the accumulation of endogenous acetylcholine. Therefore, it seems reasonable to propose that the “muscarinic” receptors in the caudate also participate neurophysiologically in a complex cholinergic mechanism regulating involuntary motor activity.

Responses to electrical stimulation of caudate nucleus in cats in chronic experiments.

Responses to electrical stimulation of caudate nucleus in cats in chronic experiments.