Abstract
BackgroundMethamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function.MethodsImmunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization.ResultsRepeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels.ConclusionsOur results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.
Highlights
Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, the dopamine system
Whereas Jitai tablet (JTT) pre-treatment attenuated these behavior responses, as the stereotype scores decreased significantly in the JTT pre-treatment group compared to that in the METH group after each METH injection (F (1, 18) first injection = 69.7, F (1, 18) second injection = 62.6, F (1, 18) third injection = 81.0, F (1, 18) forth injection = 69.4, p < 0.001). These results indicate that JTT pre-treatment could effectively attenuate the METH-induced behavior response
We found that post-treatment with a high dose of JTT completely recovered the losses in striatal dopamine transporter (DAT), D2 receptors (D2R), and tyrosine hydroxylase (TH) induced by repeated METH administration
Summary
Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, the dopamine system. PET imaging studies have reported that METH appears to induce long-lasting decreases in dopamine D2 receptors (D2R) [11] and persistent decreases of 20–30% in striatal DAT [12], and that this reduction can last as long as 3 years after METH withdrawal [8]. These neurobiological changes in the dopaminergic system are believed to contribute to the difficulties in abstinence treatment and the high relapse potential. Medications that target dopaminergic pathways are presumed to have potential for the treatment of METH abuse
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