Decrease In Acetylcholine Levels Research Articles

Effect of atropine and/or physostigmine on cerebral acetylcholine in rats poisoned with Soman

Cerebral acetylcholine (ACh) levels in normal animals were found to be 29.6 ± 1.4 (S.E.) nmoles ACh/g of wet tissue. Physostigmine and Soman reduced cerebral cholinesterase (ChE) activity to < 18% of control and increased cerebral ACh levels by 148 and 130% of normal, respectively. Neostigmine failed to alter ChE activity or ACh levels. Atropine decreased ACh levels to 62% of normal. When atropine was given with physostigmine or Soman, the ACh levels were almost normal. Soman failed to increase the levels of ACh in animals protected with atropine and physostigmine. When physostigmine was followed by Soman, cerebral ACh levels were lower than in animals given physostigmine only. Our data indicate that it may be possible to manage ACh concentrations in animals poisoned with irreversible ChE inhibitors by prior treatment with apprópriate dosages of anticholinergic and reversible anti-ChE drugs. The data also suggest that ACh and/or anti-ChEs inhibit the synthesis of ACh.

Regional differences in the sensitivity of cholinergic neurons to dopaminergic drugs and quipazine in the rat striatum

Marked differences were found in the activity of choline acetylase (ChAc) in various discrete areas of the rat striatum. The richest cholinergic innerbation was observed in the centrolateral part of the structure. A similar distribution was obtained by measuring acetylcholine (ACh) levels in punches taken from frozen frontal serial slices. As revealed by the analysis of the topographical distributions of ChAc activity, ACh, 5-HT and DA, the regional cholinergic innervation differed markedly from that of aminergic terminals. Changes in ACh levels induced by drugs could be estimated in microdiscs of tissues punched from frozen slices. Apomorphine and haloperidol, which increased and decreased ACh levels respectively, induced similar effects in the various striatal areas examined. By contrast quipazine, a drug acting on 5-HT uptake and release and on serotoninergic recptors, selectively increased ACh levels in some areas of the striatum but not in others. The regional changes in ACh levels induced by quipazine were satisfactorily correlated with the regional distribution of 5-HT but not with that of DA. These results suggest that a limited population of striatal cholinergic neurons is under the inhibitory control of serotoninergic neurons. They also indicate that some striatal cholinergic neurons influenced by dopaminergic neurons are not controlled by serotoninergic neurons.

Changes in regional brain acetylcholine levels during drug-induced convulsions

Acetylcholine (ACh) levels were determined in the brain of rats killed by decapitation or focussed microwave radiation during drug-induced convulsions. During metrazol or strychnine-induced convulsions a diffuse decrease in ACh levels was found in rats killed by decapitation. When the rats were killed by radiation and the brain was only divided into three large regions, strychnine caused no changes in ACh levels; metrazol caused a decrease in the cerebral cortex and lower brainstem. When discrete brain regions were investigated in rats killed by radiation, metrazol-induced convulsions were associated with a decrease in ACh level in all regions dissected and strychnine-induced convulsions with a decrease in the hippocampus and caudate nucleus only. Picrotoxin-induced convulsions were associated with a decrease in ACh level in the cerebral cortex, hippocampus, midbrain and medullapons, those induced by bicuculline with an increase in ACh level in the frontal cortex, hippocampus, midbrain and medulla-pons, by dimefline with an increase in the frontal cortex, midbrain and medulla-pons and a decrease in the caudate nucleus. The experiments show that each type of convulsant affects ACh levels in discrete brain regions in a different way.

Regional levels of choline and acetylcholine in rat brain following head focussed microwave sacrifice: Effect of (+)-amphetamine and (±)-parachloroamphetamine

The effect of (+)-amphetamine and (±) p-chloroamphetamine on the levels of choline and acetylcholine (ACh) in discrete regions of rat brain were studied. Animals were sacrificed by head focussed microwave irradiation which terminated all measurable enzymatic activity in brain within two seconds. Both p-chloroamphetamine and amphetamine induced short term ( < 48 hr) increases in ACh levels in the striatum and cerebellum and simultaneous decreases in ACh levels in the hippocampus and cortex. In addition, p-chloroamphetamine caused a long term (> 48 hr) increase in ACh levels in the striatum and cerebellum. It is suggested that the short-term change in ACh levels induced by p-chloroamphetamine and amphetamine are mediated via release of dopamine. while the long term changes in ACh levels caused by p-chloroamphetamine are related to serotonin and may indicate that serotonin is involved in the regulation of ACh turnover in the striatum.

Influence of noncholinergic drugs on rat striatal acetylcholine levels

Rat striatal acetylcholine levels were measured in rats following the administration of drugs that primarily affect dopamine metabolism. Reserpine, clozapine and chlorpromazine caused decreases in striatal acetylcholine levels of 33%, 38% and 54% respectively. Apomorphine, L-DOPA, methamphetamine and amantadine caused increases of 27%, 14%, 17% and 45% respectively. The decrease in acetylcholine levels following drugs that deplete or block dopamine, and the increase following drugs that enhance dopamine or stimulate its receptors, is consistent with a direct inhibitory action of dopamine on cholinergic striatal interneurons. Increased levels of acetylcholine would accompany decreased firing of cholinergic neurons due to dopaminergic inhibitory action. Decreased levels would accompany increased firing due to reduced dopaminergic inhibitory action.