The Role of 5-HT Receptors on the Acetylcholine Release from the Rat Striatum / 대한정신약물학회지

The aim of this study was to investigate the role of the 5-HT receptors in acetylcholine (ACh) release from the striatum. Slices from the rat striatum and synaptosomes were incubated with [3H]-choline and the release of the labelled products was evoked by electrical (3 Hz, 2 ms, 5 V/cm, rectangular pulses, 2 min) and potassium-stimulation (25 mM), respectively, and the influence of various serotonergic drugs on the evoked tritium outflows was investigated. Serotonin decreased the electrically-evoked ACh release in striatum in a concentration-dependent manner without the change of basal release. In hippocampal and entorhinal cortical slices, serotonin did not affect the evoked and basal release of ACh, but, at large dose (30 microM) decreased the evoked ACh release in hippocampus. 2,5-Dimethoxy-4-iodoamphetamine (DOI), a specific 5-HT 2A/2C agonist, decreased evoked ACh release in the striatum. CGS-12066A (5-HT 1B agonist), m-chlorophenyl-biguanide (5-HT 3 agonist) and 5-[(dimethyl -amino)methyl]-3-(1-methyl-1H-indol-3-yl)-1,2,4-oxadiazole (5-HT 3 antagonist) did not affect the evoked and basal ACh release in all tissues. Ritanserin, a specific 5-HT 2A/2C antagonist, blocked the inhibitory effects of serotonin and DOI, whereas, ketanserin, an another type of specific 5-HT 2A/2C antagonist did not affect the inhibitory effects of serotonin and DOI. In striatal synaptosomal preparation, serotonin and DOI did not affect the K +-evoked ACh release. These findings suggest that ritanserin-sensitive 5-HT 2A/2C receptors located in the soma and/or axons of the striatal cholinergic neurons play a important role in ACh release.

Effect of Tetrahydro-9-Aminoacridine on Acetylcholine Release in the Rat Hippocampus / 대한정신약물학회지

It is well known that the cholinergic innervation of hippocampal formation plays an important role in the process of memory and learning, and the deficit of this system might be a cause of the senile dementia including Alzheimer's disease. Several studies have suggested that increased central cholinergic activity could improve the cognitive deficits of the senile dementia. Therefore, many attempts have been made to reverse theses cognitive impairment by enhancing the central cholinergic activity through the use of cholinomimetics such as ACh precusor, cholinesterase(ChE) inhibitors and direct cholinoceptor agonists. Since Summers et al. reported that tacrine is worthy of novice as a possible palliative treatment for Alzheimer's disease, it has been shown to improve the memory and cognitive functions in some patients. Although tacrine is a potent centrally cholinesterase inhibitor, it seems unlikely that this property alone could underlie its clinical effect. Because the eserine, a specific cholinesterase inhibitor, showed little improvement in such patients, it is possible that tacrine may act in a different way to produce its clinical efforts. There are reports that tacrine blocked the some types of cation channels and the muscarinic receptors, and stimulated the nicotinic receptors in the central nervous system. After all, though a large body of experimental data have been accumulated, the mechanism controlling ACh release be tacrine still remains to be elucidated. In attempt to address the abode issue, this study was designed to delineate the action mechanism of tacrine on the electrically-evoked ACh release in the rat hippocampus.