| [BACKGROUND]Abuses of Amphetamine-type stimulants are extraordinary wide all over the world now and the utilization exceed traditional type drugs. The most extensive and representative drugs include amphetamine, methamphetamine (MA), MDMA and so on, which does harm to the community.Polydrug abuse defines using two or more psychoactive drugs in combination to acquire a particular effect. In many cases, a base or primary drug, with taking additional drugs are co-used, for reducing or compensating for the side effects of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is limited. Poly drug use often brings more risks than single drug use, because of the increase of side effects and drugs synergy. The potentiating effect of one drug on another is sometimes considerable, and here the licit drugs and medication-such as alcohol-have to be considered complecated with the controlled psychoactive substances, especially amphetamines. It possesses significant and important value for solving the forensic drug distribution to clarification postmortem distribution and redistribution of amphetamines in rats on ethanol-amphetamines polydrug use and influence of ethanol on the discipline.[OBJECTIVE]To detect the distribution of MA in vivo and postmortem redistribution of MDMA in rats in different environments regarding of ethanol-MA acute and sub-acute poly-drug use rats models and ethanol-MDMA acute poly-drug use rats models. The specific items are including the following two parts.1. To detect the blood alcohol concentration and distribution of methamphetamine (MA) in rats' models of acute and sub-acute MA-ethanol poly-drug use and distinguish the influence of ethanol on the postmortem distribution of MA in rats.2. To study the blood alcohol concentration and postmortem redistribution of MDMA in rats' models of acute MDMA-ethanol poly-drug use in 10d under different conditions and distinguish the influence of ethanol on the postmortem redistribution of MDMA in rats.[METHODS]1.36 male Sprague-Dawley rats, weighing 220 g±20 g, were divided into six groups randomly, including poly-drug acute poisoned group (group A), MA acute poisoned group (group B), poly-drug sub-acute poisoned group (group C), MA sub-acute group (group D), active drinking group (group E) and the control (group F). Group A, C and E rats were fed 20% ethanol ad libitum as the sole fluid source for 4 weeks (as adaptive phase). For the next consecutive 5 days and 14 days, these groups were treated as chronic active-drinking rats respectively. Meanwhile, the group B, D and F were given ultrapure water. Intraperitoneal injections (1.0 mg/kg·d) of 1.0 mg/mL MA solution were given to the chronic active-drinking rats and normal rats (group A and C, group B and D) over 5 days and 14 days, respectively; and the same volumes of physiological saline solution was injected to the other 2 groups (group E and F). The volumes of injection were adjusted along with rats' weight change every day. After these consecutive steps, acute and sub-acute combined abuse models were set up.0.5 h after the last injection, rats were sacrificed by cervical dislocation; and samples, including vitreous humor, peripheral blood, urine, heart, liver, spleen, lung, kidney, brain, testes and muscle, were collected immediately. Ethanol in peripheral blood was determined as soon as possible; and other samples were frozen at -80?. Concentrations of MA in samples were determined in time.2.720 male SD rats,weighing 220 g±20 g, were divided into eight groups randomly, including poly-drug acute poisoned group 1 and 2, active drinking group 1 and 2, MDMA acute poisoned group 1 and 2 and the control group 1 and 2. In these groups, the series "1" rats were kept at 25?with humidity 70%, while the series "2" rats were at 4?with humidity 50%. The poly-drug acute poisoned group 1 and 2, active drinking group 1 and 2 rats received 20% ethanol-water ad libitum as the sole fluid source for 4 weeks (as adaptive phase) which produced these groups'chronic active-drinking rats respectively. Meanwhile, the MDMA acute poisoned group 1 and 2 and the control group 1 and 2 were given pure water. Oral administrations of MDMA (150 mg/kg) were given to poly-drug acute poisoned group 1 and 2 rats and MDMA acute poisoned group 1 and 2 rats; while models of acute poly-drug poisoned rats, based on oral administration of normal saline to MDMA acute poisoned group 1 and 2 and the control group 1 and 2. All the rats were put to death and kept left lateral position. Ethanol in heart bloods were determined when rats were put to death. Samples, including vitreous humor, heart blood, urine, heart, liver, spleen, lung, kidney, brain, testis and muscle, were collected at 0 h,2 h,4 h,10 h,18 h,24 h,2 d,3 d,4 d,5 d,6 d,7 d,8 d,9 d and 10 d and preserved sealed at -80?; and then the concentrations of MDMA were detected timely.3. Compared the postmortem distribution of MA and redistribution of MDMA in rats of poly-drug acute poisoned group and MA acute poisoned group, poly-drug sub-acute poisoned group and MA sub-acute poisoned group, MDMA-ethanol poly-drug acute poisoned group 1 and 2, MDMA acute poisoned group 1 and 2 at corresponding time point. Multi-way classification analysis of variance and Bonferroni test were developed to analysis the influence of ethanol on MA distribution in acute and sub-acute poly-drug use rats and MDMA postmortem redistribution in acute poly-drug use in 10 d at at 25?, humidity 70% and 4?, humidity 50%. Summarize the influence of ethanol on postmortem distribution and redistribution of ATS, such as MA and MDMA, under different conditions, by different manners of death.[RESULTS]1. The blood alcohol concentrations did not display significant differences among the group A, C and E. After being repeated intraperitoneal injections, MA mainly concentrated in liver, lung, kidney and brain of rats of group A, B, C and D; meanwhile, MA was detected in other body fluids and tissues at different levels. The concentrations of MA of body fluids and tissues in rats of group C and D were higher than those in group A and B; and the concentrations of MA in rats of group A and C were higher than the ones of group B and D.2. The blood alcohol concentrations displayed no significant differences among the poly-drug acute poisoned group 1 and 2, active drinking group 1 and 2. After being repeated oral administration of MDMA (150 mg/kg), MDMA mainly concentrated in liver, lung, kidney and brain of rats of poly-drug acute poisoned group 1 and 2 and MDMA acute poisoned group 1 and 2; meanwhile, MDMA was detected in other body fluids and tissues at different levels. From 0 to 10 day at 25?with humidity of 70% and 4?with humidity of 50%, the concentrations of MDMA in body fluids and tissues changed at different levels. At room temperature, the MDMA levels of vitreous humor, heart blood, urine, heart, liver, spleen, lung, kidney, brain, testis and muscle of rats of MDMA acute poisoned group 1 showed elevating, and then decreasing associated with various degrees. The tendency of MDMA levels change of samples of MDMA acute poisoned group 2 was less noticeably while the bodies were kept at 4?. Under the same condition, the tendency to concentration of poly-drug acute poisoned group 1 and 2 rats was similar to the MDMA acute poisoned group 1 and 2 rats with lower extent and advanced turning point. The changes of PMR concentrations in body fluids and tissues were found significant differences.3. The concentrations of MA in body fluids and tissues of rats in group A and C were higher than group B and D. At 25?with humidity of 70%, the variation tendency of MDMA in rats of poly-drug acute poisoned group 1 were similar to MDMA acute poisoned group 1 with lower degree and advanced turning point. The variation tendencies of MDMA in rats of poly-drug acute poisoned group 2 were similar to MDMA acute poisoned group 2 with lower degree and advanced turning point as well at 4?with 50% humidity.[CONCLUSIONS]1. After multiple times of injections, the concentration of MA in samples of sub-acute intoxicated rats were higher than the concentration in acute intoxicated rats, which means injection frequency might cause residue at different degree in different samples, no matter poly-drug use or mono-drug addict. The levels of MA in samples of acute and sub-acute poisoned poly-drug use rats were higher than the levels in acute and sub-acute poisoned mono-drug use rats. Ethanol could accelerate the absorption of MA and increase the concentration due to poly-drug use while the tendency to change depended on the categories of samples; but it has nothing to do with the residue caused by increase of times of injections.2. No matter poly-drug use or mono-drug addict, lower temperature might reduce the PMR of MDMA in body fluids and tissues. Combined ethanol could accelerate the PMR of MDMA in samples while poly-drug use at a certain degree. And the extent of acceleration in body fluids and tissues were different according to sample feature; meanwhile, lower temperature might reduce the influence of ethanol on PMR of MDMA in samples. |
PDF Full Text Request