Researches On The Relations Between Toluene Inhalation & Mice Neurotoxicity And Addiction

Background and objectiveToluene is one of the lipid soluble central nervous system depressant with small molecular mass, which can overpass blood-brain-barrier easily. According to recent researches on it, after being inhaled, toluene could be absorbed easily, spread into the brain and give ramification on the cell membranes of the nervous system, thus leading to abnormal nervous symptoms such as: neurotoxicity which dominates a series imbalances of cognition, movements, and postures and rewarding effectiveness and rewarding effect which dominates a series physiological and psychological dependence movements [1,2].With the yearly increasing amount on toluene production and consumption, the environment and neurotoxicity problems brought about by toluene are catching the eyesights of people around the world. In some countries and regions, especially in some underdeveloped countries, toluene has already become one of the popular inhaled abused drugs and doubtlessly has become a social concern. As a inhaled neurotoxic drug, neurotoxicity and addiction mechanisms of toluene are still unknown. The researches on this test is to deepen into the effect and mechanisms of toluene neurotoxicity and addiction through ethological and morphology studies. Section one: The observations on Kunming mice's neuroethology and addiction behaviors through toluene inhalation in different dosesMethods Through comparing the different behavioral changes through toluene inhalation in different doses in neuroethology aspect, five level doses were chosen as followings: 1.21,2.42,4.84,9.68,19.36㎎/L with the interval 20min/d×5d. Through the ethological methods, the changes of autonomic activities, the degraded learning-and-memory ability and the conditioned place preference were detected.ResultsThe autonomic activities were observed to increase obviously of the group inhaling 2.42,4.84㎎/L compared with the control group(P<0.05), while that of the group inhaling 19.36㎎/L showed obvious decrease compared with the control group(P<0.05); The latent periods in the water maze of the group inhaling 19.36㎎/L was prolonged obviously compared with the control group (P<0.05) without too much changes on the frequencies of the mice getting to the dead end(P<0.05). Compared with that group, the other three groups: 2.42,4.84,9.68㎎/L had CPP toward toluene. (P<0.05)Section Two: The observations on the relations between age and neuroethology addiction behaviors through toluene inhalation in different doses MethodsTo compare the ramification on the rewarding effect on kuming mice of four groups in four intervals: PND(postnatal days,PND)21-25,PND31-35,PND41-45,PND56-60. Each group were subgroup into four in different doses : 2,5,10,20㎎/L and the rewarding effect were detected during the adolescence development.ResultsThe mice in juvenile of group PND25 5㎎/L showed CPP when inhaling 5㎎/L toluene. However no obvious changes could be observed in other doses. The other goups:5,10,20㎎/L(PND35) relatively in different subgroups:2,5,10,20㎎/L(PND45)could be observed to show CPP. However, there were no obvious changes in other doses. PND60 in different doses: 5,10㎎/L could show obvious CPP, however, there were no obvious changes in other doses.Section Three: Toluene neurotoxicity and addiction through ethological and morphology studiesMethods:The results of observing space learn-and-memory neuroethology addiction behaviors showed that the prescription of toluene inhalation could lead to obvious changes of autoactivity, space learn-and-memory and CPP. To observe the relations between the changes of neuroethology and addiction and neurotransmitter, the time-changing relations between CHAT,GABA and GLU positive cells in different encephalic regions and toluene inhalation,thus,the neurotoxicity and addiction mechamism could be further explored.Results:CHAT positive cells mainly spreading in the cerebral cortex showed no obvious change between different groups after 1d and decreasing number of positive cells after 6d and 14d. GABA were expressed weak expressing mainly in cerebral cortex and hippocamp and showed no obvious change between different groups after 1d and decreasing number of positive cells after 6d and 14d. GLU positive cells mainly spreading in the cerebral cortex showed no obvious change between control group after 1d and decreasing number of positive cells after 6d and 14d.Conclusion (1)Toluene in high level dose could harm the mice learn-and-memory capability.(2)Toluene in high level dose could lead mice to show psychological dependence.(3)Adolescence is the key age for mice to form toluene addiction.(4)The zoogenic growth and development (esp: that of nervous system) has some relations with the sensitivity of toluene addiction.(5)Neurotoxity and addiction have something to do with the changes of some neurotransmitters such as: ChAT,GLu in cerebral cortex and hippocamp...