Alleviation of Methamphetamine Sensitization by Partially Lesioning Dopaminergic Terminals with 6-Hydroxydopamine in Nucleus Accumbens

Abstract

Amphetamine-type stimulants have become important and popular abused drugs worldwide. Methamphetamine (Meth) sensitization, characterized by a progressive increase in behavioral responses after repeated administration, has been reported in rodents and patients. This behavioral effect has been used as a laboratory model to study drug addiction and schizophrenia. The mesolimbic dopaminergic pathway plays a significant role in the development of Meth behavioral sensitization. Previous studies have reported that the ablation of nucleus accumbens (NAc) by electrolytic or thermal lesioning attenuates addictive behavior to opioids in animals. However, these studies were only conducted in opioid addictive rodents. Furthermore, these ablation procedures also damaged the non-dopaminergic neurons and fibers passing through the NAc. The purpose of this study was to examine the therapeutic effect of NAc lesioning by a selective dopaminergic toxin in Meth-sensitized animals. Adult mice received repeated administration of Meth for 7 days. Open-field locomotor activity and stereotype behavior were significantly increased after Meth treatment, suggesting behavior sensitization. A partial lesion of dopaminergic terminals was made through stereotaxic administration of dopaminergic toxin 6-hydroxydopamine (6-OHDA) to the NAc in the Meth -sensitized mice. Meth behavioral sensitization was significantly antagonized after the lesioning. Brain tissue was collected for qRT-PCR analysis. Repeated administration of Meth increased the expression of tyrosine hydroxylase (TH), BDNF, and Shati, a marker for Meth sensitization, in the NAc. Treatment with 6-OHDA significantly antagonized the upregulation of TH and Shati. Taken together, these data suggest that local administration of 6-OHDA mitigated Meth sensitization in chronic Meth-treated animals. Our data support a new surgical treatment strategy for Meth abuse.

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System

“…In addition, we confirmed that 25D-NBOMe increased the expression level of TH, an enzyme that catalyzes the synthesis of catecholamines, including DA. Since psychostimulants, including methamphetamine, increase DA release in the NAc, it can be considered that repeated administration of psychostimulants increases TH expression in the NAc. , Taken together, these results demonstrate that 25D-NBOMe exhibits rewarding and reinforcing effects by inducing dopaminergic protein changes, similar to other addictive drugs.…”

Downregulation of microRNA‐330‐5p induces manic‐like behaviors in REM sleep‐deprived rats by enhancing tyrosine hydroxylase expression

“…In contrast to PD animals, in manic‐like SD rats, we observed an increase of TH expression through the reduction of miR‐330‐5p in the prefrontal cortex. A previous study also showed an increase of TH expression in the nucleus accumbens of methamphetamine‐treated mice, which are considered a model for mania, schizophrenia, and addiction, showing enhanced synaptic dopamine levels 50 . Interestingly, injection of dopaminergic toxin 6‐hydroxydopamine (6‐OHDA) antagonized the increase of TH in methamphetamine‐treated mice 50–52 .…”

“…A previous study also showed an increase of TH expression in the nucleus accumbens of methamphetamine‐treated mice, which are considered a model for mania, schizophrenia, and addiction, showing enhanced synaptic dopamine levels. 50 Interestingly, injection of dopaminergic toxin 6‐hydroxydopamine (6‐OHDA) antagonized the increase of TH in methamphetamine‐treated mice. 50 , 51 , 52 6‐OHDA is also a neurotoxin used to produce Parkinsonism rodent models.…”

“… 50 Interestingly, injection of dopaminergic toxin 6‐hydroxydopamine (6‐OHDA) antagonized the increase of TH in methamphetamine‐treated mice. 50 , 51 , 52 6‐OHDA is also a neurotoxin used to produce Parkinsonism rodent models. 53 , 54 Considering these previous reports and our results, the delicately balanced regulation of dopamine transmission including TH may play an important role in the drug therapy of PD, schizophrenia, and BPD.…”

Osteoclastogenesis Inhibitor and Antioxidant Properties of Konjac Glucomannan in a Periodontitis Mice Model: An In Vivo Study

“…The primer sequences for the OPG were as follows: forward, 5′-AGC AGG AGT GCA ACC GCA CC-3′ and reverse, 5′-TTC CAG CTT GCA CCA CGC CG-3′ [ 23 ]. The primer sequences for glyceraldehyde-3-phosphate dehydrogenase were as follows: forward, 5′-CAT CAC TGC CAC CA GAA GAC TG-3′ and reverse, 5′-ATG CCA GTG AGC TTC CCG TTC AG-3′ [ 24 ].…”