Alterations in COMT gene expression in the spinal cord of male rats during buprenorphine treatment in methamphetamine-induced addiction

Background and Aim : Substance abuse is a universal health and social problem. Amphetamine (AMPH) exerts its rewarding and reinforcing effects by elevating extracellular dopamine which plays an important role in drug reward. The critical mechanism to control the levels of synaptic dopamine is the degradation of dopamine by the enzyme Catechol- O-methyltransferase (COMT). The COMT is an important enzyme to metabolize catechol neurotransmitters such as dopamine and regulates the level of dopamine. Buprenorphine is a weak partial mu-opioid receptor agonist and a weak kappa-opioid receptor antagonist used for the treatment of severe pain. It is also commonly used as an alternative to methadone for the treatment of severe opioid addiction. The aim of this study was to investigate the alterations of COMT gene expression during methamphetamine-induced addiction and treatment with buprenorphine 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 COMT gene using real time polymerase chain reaction method (RT- PCR).Results : Chronic administration of methamphetamine increased the COMT gene expression in comparison to control group (p<0.001). Acute and chronic administration of buprenorphine increased the level of COMT in comparison to control group (p<0.01 and p<0.001 respectively). In Spontaneous methamphetamine withdrawal syndrome group, the level of COMT gene expression did not changed in comparison to control group, but in comparison to methamphetamine group decreased and approached to the level of control group.Conclusion : The COMT enzyme is a major regulator of the synaptic dopamine levels and plays an important role in dopamine catabolism. It seems during amphetamine addiction because of increasing dopamine in synaptic cleft, the regulation of COMT gene expression is changed. May be this would be a compensatory mechanism for removal of excess dopamine.

کلیدواژه ها:

COMT ، Methamphetamine ، Buprenorphine