| Objective:To establish Methamphetamine dependence rat model, then detected the expression of acetylcholinesterase(ACHE) and acetylcholine transferase(CHAT) in cognitive-related brain regions of the prefrontal cortex(PFC), medial septal nucleus(MS), Meynert basal ganglia(MBN), hippocampus(HP) and Addiction-related brain striatum (CPu), nucleus accumbens (NAc), interpeduncular nucleus (IPD). Discussed The relations between the changes of above two indicators and memory and cognitive impairment caused by Methamphetamine (MA) and the relation between the changes of the two indicators and the mechanism of MA dependence.Methods:50 Strague-Dawley rats were divided into five groups which were control group,1 week group,2 weeks group,4 weeks group and 8 weeks group of administration methamphetamine. experimental group rats were administered with MA by intraperitoneal injection 10mg·kg-1 per day and the control group were administered with the same dosage saline. Each group were conducted conditioned place preference test and then observed the stereotypic behavior after the last dose. After successful established rats model of MA dependence, Immunohistochemistry were applied to detect the expression of ACHE and CHAT in above brain regions, and then did an quantitative analysis.Results:Compared with the control group, the conditioned place preference test of four experimental groups were differences (P＜0.05). The rats administration with MA expressed obvious stereotyped behaviors. The expression of ACHE and CHAT showed no difference compared with control group in each group of cognitive-relative brain regions of the PFC, MBN (P＞0.05). In the MS region, the expression of ACHE maintained a low state for administration of MA 1-8 weeks(P＜0.05) and the expression of CHAT showed no difference compared with control group(P＞0.05). In the HP region, the expression of ACHE and CHAT was decreased for administration of MA one week, lower than the control group (P＜0.05), then returned to normal. In the addiction-related brain regions of the CPu and NAc,the expression of CHAT were decreased after administration MA for one week(P＜0.05),then returned to normal. The expression of CHAT was increased on administration MA tow weeks (P＜0.05), then returned to normal. In the IPD region, the expression of ACHE had risen for administration 4-8 weeks. The lever of ACHE expression of 8 weeks group was higher than normal lever (P＜0.05). The expression of CHAT of each group showed no difference compared with control group in the IPD region (P＞0.05).Conclusion:1. Administered rats with MA by intraperitoneal injection and combined with a conditioned place preference test and stereotyped behaviors score successfully established rat model of methamphetamine dependence.2. he expression of ACHE and CHAT tended to be normal in the cognitive-related brain regions of the CPu, MBN, HP. In the MS region, the expression of ACHE was deceased and the expression of the CHAT was in normal. Cholinergic neuronal function was in normal or enhanced state. Cognitive-related brain regions cholinergic neurons had no significant toxic damage after administration with MA. MA causes memory and cognitive function impairment is unrelated to central cholinergic neurons dysfunction. 3. In the addiction-related brain regions CPu, NAC, the expression of CHAT was decreased within 1-2 weeks, then the expression of the ACHE was increased. The cholinergic neuronal function in suppressed. The suppression of cholinergic neuronal function may be related to the mechanisms of methamphetamine dependence. After four weeks of cholinergic neurons function returned to normal levels may be related to the mechanisms of resistance after Long-term using MA. In the IPD brain region, cholinergic neuronal function is inhibited after administration with MA for 8 weeks, that may be the second cholinergic mechanism related to drug resistance.
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