Investigating the dopamine and monoamine oxidase gene expression during amphetamine addiction in male rats who were under treatment with buprenorphine

Background and Aim : Amphetamine is an indirect dopamine agonist that promotes release of dopamine from vesicles and attenuates dopamine reuptake. Amphetamines are similar in structure to dopamine, and so can enter the presynaptic neuron via its dopamine transporters. By entering, amphetamines force dopamine molecules out of their storage vesicles. By increasing presence of dopamine both these lead to increased pleasurable feelings and addiction. Monoamine oxidases (MAO-A and MAO-B) are mitochondrial enzymes that oxidatively deaminate endogenous biogenic amine neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine. Buprenorphine, a partial agonist at the mu opioid receptor, is licensed and widely used in many countries for the treatment of acute and chronic pain. Buprenorphine is also well established for the treatment of opioid dependence. The purpose of this study was to examine the acute and chronic effect of buprenorphine on the level of dopamine and MAO gene expression during methamphetamine-induced addiction in the spinal cord of male rats.Methods : 84 male Wistar rats were randomly assigned into 12 experimental groups (n=7): Control, Saline, Methamphetamine (10 mg/kg, i.p. for 5 days), buprenorphine (6, 10 mg/kg, i.p.), methamphetamine+ buprenorphine with 2 doses for 5 and 14 days and Spontaneous methamphetamine withdrawal syndrome (72 hour later). The lumbar section of spinal cord tissue was assayed for the expression of dopamine and MAO gene using RT- PCR.Results : Chronic administration of methamphetamine to control group increased the dopamine gene expression in comparison to control group (p<0.05). Acute administration of buprenorphine in both doses increased the level of dopamine (p<0.05). Chronic administration of buprenorphine did not have significant effect. In the spontaneous methamphetamine withdrawal syndrome group, the level of dopamine gene expression decreased in comparison to control and addicted group, but statically it was not significant. Also there was not any significant alteration in the level of MAO between groups.Conclusion : The present work shows that methamphetamine toxicity increased the level of dopamine gene expression. Acute and chronic treatment of buprenorphine gently reduced this increase and tried to approach it to the control level. It seems the dose and the time course of methamphetamine and buprenorphine which are introduced in this study did not have enough potency to alter MAO gene expression.

کلیدواژه ها:

Dopamine ، Monoamine Oxidase ، Methamphetamine ، Buprenorphine