Study On The Correlation Between Brain IEG And Morphine Psychological Dependence In Rat

1 ObjectiveDrug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences. Addictive substances induce pleasant states (euphoria in the initiation phase) or relieve distress. Continued use induces adaptive changes in the central nervous system that lead to tolerance, physical dependence, sensitization, craving, and relapse. Long-term administration of addictive drugs produces alterations in the brain that increase vulnerability to relapse and facilitate craving even months or years after successful detoxification.Immediate early genes are a class of genes whose expression is induced within minutes of exposure to a stimulus. Of particulai: interest in the study of addiction are the Fos and Jun families of immediate early genes, which encode transcription factors. The Fos family of transcription factors includes c-Fos, FosB, Fos-related antigens 1 and 2 (Fra-1 and -2), and AFosB.Transcription factors encoded by the fos and jun families of immediate early genes also have been studied as potential mediators of drug-induced neural plasticity. Acute administration of stimulants or opiates rapidly but transiently induces several Fos- and Jun-like proteins in the nucleus accumbens and related striatal regions. Immediate-early genes (IEG) and their protein products act as transcription factors and therefore can influence the expression of other genes. Because of this ability, activation of IEGswithin a neuron indicates that a response has been elicited by a particular stimulus. Because the IEG c-Fos is expressed at very low levels in the unstimulated brain, it has been used to show the activation of brain regions in response to different stimuli, including many drugs of abuse. Previous studies have shown that many drugs of abuse, including opioids, induce immediate-early gene expression, c-fos, and the expression of its protein product the transcription factor Fos have been proposed to reflect second messenger activation and to serve as sensitive indicators of neuronal activation, leading to longer term adaptive responses mediated by the regulation of other delayed response genes. However, the different phases under CPP model showing c-Fos expression has not been determined.In contrast, chronic drug exposure desensitizes the ability of these proteins to be induced and results instead in the gradual accumulation of novel Fos-like proteins, termed chronic FRAs (Fos-related antigens). Recent work has definitively identified the chronic FRAs as isoforms of AFosB, a truncated splice variant of FosB. The AFosB isoforms accumulate in brain after repeated drug treatment as a result of their extraordinary stability and thereby are ideal candidates to serve as molecular switches for relatively long-lived adaptations to drug exposure. AFosB isoforms are very stable and demonstrate in vivo half-lives of weeks. They therefore persist for weeks after the drug is withdrawn. As a result, AFosB levels gradually accumulate with repeated drug exposure, suggesting that its dynamics allow it to play a longer-term role in subsequent regulation of gene expression. Second, AFosB expression is significantly induced in response to chronic exposure to several drugs of abuse, including cocaine, amphetamine, opiates, nicotine, ethanol, and phencyclidine. Because of its unique temporal properties and its induction by virtually all drugs of abuse, the functional significance of AFosB in drug-related behaviors has been studied extensively.A major goal of current research is to determine whether the c-Fos and AFosB induced in the brain during CPP difference phase (CPP acquisition , extinction, reinstatement) and to identify the change of c-Fos and AFosB protein expression in PFC, NAc, HPC based on the CPP model.2 Meterials and Methods2.1 Animals:Male Sprague Dawley rats (Zhejiang Medical Science College, China. Initial weight 200-220 g) were housed four per cage. The room temperature was kept at 23±1℃, and a 12-h light-dark cycle (lights on at 7 p.m.) was maintained...