Our previous studies on cannabinoid type1 receptor (CB1R) activation on Methamphetamine (METH)-induced neurodegeneration and locomotion impairments in male rats suggest an interaction between CB1Rs and METH. However, the role of these receptors in METH-neurotoxicity has not been fully identified. Therefore, the purpose of the present study is to investigate the involvement of CB1Rs in these effects. We conducted an electrophysiological study to evaluate functional interactions between METH and CB1Rs using whole-cell patch current clamp recording. Furthermore, we designed the Nissl staining protocol to assess the effect of METH on the basic cerebellar Purkinje cell structure. Our findings revealed that METH significantly increased the action potential half-width, spontaneous interspike intervals, first spike latency, and decreased the rebound action potential and spontaneous firing frequency. Using CB1R agonist and antagonist, our results showed a significant interaction with some of the electrophysiological alterations induced by METH. Further, Nissl staining revealed that the exposure to the combination of METH and SR141716A resulted in the necrotic cell death. Results of the current study raises the possibility that METH consumption profoundly affect the intrinsic membrane properties of cerebellar Purkinje neurons and cannabinoid system manipulations may counteract some of these effects. In summary, our findings provide further insights into the modulatory role of the endocannabinoid system in METH-induced neurologic changes, which can be used in the development of potential therapeutic interventions for METH dependence.
Background:Recent studies have shown that addiction may be caused by abnormality of neurotransmission in the brain. Two neurotransmitters that involve into morphine addiction are dopamine and glutamate. The glutamatergic and dopaminergic systems are also involved in morphine tolerance and morphine withdrawal syndrome signs. Ascorbic acid (AA), as the antioxidant releases from the glutamatergic neurons, modulates the action of the dopamine and glutamate systems. In this study, the effect of AA on morphine self-administration and morphine withdrawal symptoms has been investigated.Materials and Methods:Male Wistar rats (250 - 300g) were anesthetized with ketamine (11%) and xailazine (15%). The cannula was inserted into the right jugular vein, and it was fixed subcutaneously on the skull. After surgery the animals were placed in individual home cages, and they were allowed to recover from the operation for five days, before the test. The animals were subjected to self-administration morphine for12 consecutive days, two-hour/sessions. The number of infusions and number of active and passive lever pressings were recorded.Results:An intra peritoneal injection of Ascorbic acid (AA) (400 mg/kg, i.p.), 30 minutes before morphine self-administration, produced a significant decrease in 12 days self-administration of morphine and withdrawal syndrome signs (P < 0.05). The morphine withdrawal signs (MWS) were recorded after naloxone precipitation, which decreased significantly with the injection of AA (400,700mg/kg), (<0.05). The number of self-infusions and the number of active lever pressings had significantly decreased after AA injection (P < 0.05).Conclusion:The chronic administration of AA may prevent the development of tolerance and physical dependence on morphine self-administration via the glutamatergic system.
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