Alcohol Establishment And Improvement Of The Rat Dorsal Striatum Long-term Synaptic Inhibition Of Rat Brain Slices, Extracellular And Intracellular Current Clamp Recording Technique,

Alcohol dependence ( alcohol addiction), as a psychiatric disorder, affects approximately 13% of the population at some point in life. Approximately half of all homicides and motor vehicle related deaths involve alcohol, as do one fourth of all suicides. The estimated social impact of alcohol dependence is $100 billion in health care costs, lost wages, and family disruption. Researchers are studying alcoholism from the sociological to the molecular level. A few research areas include the neurobiology of craving and tolerance, changes in cortical neurochemistry with dependence and withdrawal, and the development of medications to reverse intoxication and to prevent craving.The main pharmacological effects of alcohol are inhibiting the glutamate N-Methyl-D-aspartate (NMDA) receptor and facilitating the gamma-aminobutyric (GABA) receptor sub type A. Alcohol also has effects the membrane receptors and ionic channels such as 5-HT3 receptor and L type Calcium channel. The central neural system will adapt to compensate the effects of alcohol when dependence and withdrawal, and this is the basis of alcohol tolorence and withdrawal symptoms. However, like other drugs of addiction (such as herion, cocaine and amphetamine), even after treatment and a long period of abstinent, the risk of relapse remains high.There is evidence that drug addiction in human and animals is involve learning and memory mechanism. And conditioned reflex also involved in the establishing of drug-searching and drug-taking behaviors. These 'behavioral learning' and 'habit learning' could persist for a long time after abstinence. This may be the key point of relapse in neural system.The striatum is a very important nuclear of the basal ganglion. It is divide into the dorsal striatum and the ventral striatum(NuclearAccumbens). The Nacc is the key area of the reward effect of neural system. The dorsal striatum palys an important role in performing movement and establishing habit behaviors. Alcohol could stimulate the Nacc to produce reward effect, and this is the positive reinforcement of alcohol addiction. Alcohol also has effect on the dorsal striatum and influence the formation of drug-taking and drug-seeking behaviors.This study first establish the method of the induction of long-term depression (LTD) in the dorsal striatum of rats. Investigate the effect of alcohol on the synaptic plasticity in striatum. Sprague-Dawley rats was used and coronal brain slice including striatum were prepared, we use a bipolar tungsten electrode to stimulate the cortex-striatum pathway and record population spike in the dorsal striatum area. High frequency stimulation (HFS) was delivered to induce LTD in the dorsal striatum. Alcohol (60mmol/L) and NMDA receptor antagonist MK-801 were pretreated before the delivery of HFS to investigate the mechanism of the effect of alcohol on the synaptic plasticity in the striatum.In control slice we found a significant LTD after HFS, the PS amplitude was reduced to 20% of the value before HFS and persistented at least 60min. When pretreated 60mmol/L alcohol 10min before HFS there was still a reduction of the PS amplitude but it was recovered slowly to 80% of the control in about an hour. Pretreated MK-801 block the induction of LTD.Conclusion: NMDA receptor may play a key role in the induction of LTD in the striatum. Alcohol can not block LTD in the striatum but it will shorten the period of LTD.