The Molecular Mechansims Of Methamphetamine Inducing Acute Actions

Methamphetamine (methamphetamine, METH) is synthetic drug, belongs to mphetamine, pure white crystals, generally called ice, often used as stimulant use. It mainly acts in the central nervous system, makes organisms to generate excitement, euphoria and hallucinogenic properties, leads to addiction after repeatedly taking. Long term use of methamphetamine leads to change dopamine signal pathways, neuron abnormal and neurodegenerative disease.The short term use of methamphetamine can cause dopamine signal change, however its mechanism is still unclear. Thus, the aim of this study is to explore acute actions of METH and to definite the mechanisms on METH addiction.Long term use of METH can cause changes of cellular signaling molecules, such as dopamine (dopamine, DA), dopamine receptors (dopamine receptor, DR), dopamine transporter (Dopamine transporter, DAT), cyclin-dependent kinase 5 (Cyclin-dependent kinase 5, CDK5), and cyclic adenosine monophosphate regulated phosphoprotein -32 change (dopamine and cAMP-regulated phosphoprotein of mass-32, DARPP-32).The neurotransmitters are closely related to complicated functions of brain. Dopamine (dopamine, DA) is one of the neurotransmitters, has multifunctions and plays roles in behavior, cognitive function, and rewarding effects. DA plays a variety of functions by binding dopamine receptors (dopamine receptor, DR). DR expression in the distribution of brain region is inconsistent, and is divided into D1-like receptor and D2-like receptor based on the difference of subunits. Dopamine transporter (dopamine transporter, DAT) is typical membrane protein and located on presynaptic dopaminergic neurons, re-uptakes DA in synaptic cleft, regulates DA concentration in the synaptic cleft and finally regulates the physiological fubctions of the central nervous system.The thioredoxin-1 (Trx-1) is extensively exsisted in organisms, regulates the redox balance and activity of transcription factor and inhibits apoptosis.Ventral tegmental area (VTA), nucleus accumbens (NAc) and prefrontal cortex are important areas in brain, are related with reward responses.This paper used a common model of dopaminergic neuron rat pheochromocytoma tumor cell line (PC 12) as subjects. We used METH to stimult PC 12 cells for short time and to detect expressions of Trx-1 and its related molecules. The study found that 10 μM METH induced the expressions of Trx-1 CDK5, DARPP32 in PC12 cells, were significantly increased at 2 h, however, the expressions of D1R, TH, MAO had no significant changes, the expression of D2R was increased significantly at 12 h and 24 h.The C57BL/6 mice were divided into four groups:wild type control group (C), methamphetamine group (M), h-Trx-1 overexpression transgenic group (TG), h-Trx-1 overexpression transgenic with methamphetamine group (TG+M). The methamphetamine was administrated to mice by intraperitoneal injection for 4 h, brain tissues were harvested. The expressions of Trx-1 and DIR in the VTA, PFC, NAc were increased, at the same time, the expressions of DARPP-32 and D2R were significantly decreased.In conclusion, acute METH stimulation could regulate expressions of DIR, D2R, and DARPP-32. Trx-1 had the role in regulating changes of these molecules. Thus, further studying mechanisms on Trx-1 regulating action of METH will provide a theoretical basis for METH addiction withdrawal treatment.