Effects of terguride on protein and mRNA expressions of dopamine D2 receptor and dynorphin in different brain regions of rats after heroin self administration / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To study mechanisms of terguride on the treatment of herion dependence. METHODS Adult male SD rats were randomly assigned into 5 groups normal control group, saline treatment during heroin use period group, terguride treatment during heroin use period group, saline treatment during heroin reinstatement period group, terguride treatment during heroin reinstatement period group, the last 4 groups established heroin intravenous self administration and cue induced reinstatement models, and after interfernce and perfusion to get the following five brain regions [including ventral tegmental area (VTA)]sections. The expression of dopamine D2 receptor protein and mRNA, prodynorphin protein and preprodynorphin mRNA was detected by immunohistochemistry and hybridization in situ. RESULTS The expression of dopamine D2 receptor was downregulated during heroin use period and upregulated during heroin reinstatement period in nucleus accumbens shell (AcbSH) region, the expression of dopamine D2 receptor mRNA was parallelled with the protein expression approximately, terguride could downregulate the high expression of receptor protein during reinstatement. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin reinstatement period in central nucleus amygdalae (CeA) region, and terguride could downregulate this high expression. The expression of dopamine D2 receptor protein and mRNA was upregulated during heroin use period and downregulated during heroin reinstatement period in CA1 region of hippocampus and prefrontal cortex (PFC), terguride could downregulate the high expression of mRNA during heroin reinstatement period. The expression of dynorphin protein and mRNA was upregulated during heroin reinstatement period, terguride could downregulate this high expression. The expression of dynorphin protein was upregulated during heroin reinstatement period, and terguride could downregulate this high expression. CONCLUSION The activity of mesolimbic dopamine is boosted up during heroin use period and depressed during reinstatement period, terguride can regulate this dysregulation. The activity of dynorphin is boosted up during cue induced reinstatement, and terguride has the downregulation effect. So the preclinic study demonstrated that terguride has the potential benefit in heroin dependence.