Neuroscience letters
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Neuroscience letters · Apr 2011
Periodic transmeningeal muscimol maintains its antiepileptic efficacy over three weeks without inducing tolerance, in rats.
Periodic transmeningeal administration of muscimol into the neocortical epileptogenic zone via a subdurally implanted device has been proposed for the treatment of intractable focal neocortical epilepsy. It is unknown whether such muscimol applications induce tolerance. The purpose of this study was to determine whether daily transmeningeal (epidural) muscimol applications into the rat parietal cortex induce tolerance to the antiepileptic effect of this drug. ⋯ This antiepileptic action did not diminish over time and was maintained throughout the 3-week test period. When muscimol was replaced with saline, the subsequent Ach administrations induced EEG and behavioral seizures. These results suggest that periodic transmeningeal administrations of a relatively low concentration of muscimol into the neocortex over three weeks do not induce tolerance to the localized antiepileptic effects of this drug.
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Neuroscience letters · Apr 2011
Analgesic effect of intrathecally γ-aminobutyric acid transporter-1 inhibitor NO-711 administrating on neuropathic pain in rats.
To investigate the analgesic effect of intrathecally administered γ-aminobutyric acid (GABA) transporter-1 inhibitor NO-711 on the sciatic nerve chronic constriction injury (CCI) rats. 5 days after intrathecal catheter placement, neuropathic pain model was established by CCI of sciatic nerve on rats. Withdrawal thresholds for mechanical allodynia and latency for thermal hyperalgesia were measured in all animals. ⋯ After intrathecal NO-711 administration, withdrawal thresholds and latency were significantly increased on CCI rats compared with control group after 1 day. The results show that GABA transporter-1 inhibitor could effectively develop analgesic effect in sciatic nerve CCI rats' model.
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Neuroscience letters · Apr 2011
Activation of the spinal extracellular signal-regulated kinase 5 signaling pathway contributes to morphine physical dependence in rats.
The activation of mitogen-activated protein kinases (MAPKs) has been observed in synaptic plasticity processes of learning and memory in morphine dependence. However, the role of extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, has not been studied yet in morphine dependence. To identify the function of ERK5 in the formation and development of morphine physical dependence, morphine withdrawal-like behavioral test and western blot technique were used in this research. ⋯ Intrathecal injection of BIX02188, a novel specific inhibitor of mitogen-activated protein kinases kinase 5 (MEK5), produced a dose- and time-dependent inhibition of the activation of spinal ERK5, without affecting activation of other MAPKs. Moreover, selective attenuation of spinal p-ERK5 expression by BIX02188 could significantly relieve morphine withdrawal symptom, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in the spinal cord. These findings suggested that activation of the ERK5 signaling pathway might contribute to morphine physical dependence and its specific pharmacological inhibitor BIX02188 could be a potential therapeutic choice for alleviation of morphine withdrawal symptoms in the future.
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Neuroscience letters · Apr 2011
White matter impairment in heroin addicts undergoing methadone maintenance treatment and prolonged abstinence: a preliminary DTI study.
Methadone maintenance treatment (MMT) might cause the impairments of neuropsychological and neurotransmitter function in opioid addicts. Whether long-term MMT could lead to the impairment of white matter (WM) in heroin addiction brain is unclear. This study compared the WM integrity in the bilateral frontal lobe, temporal lobe, splenium and genu of corpus collasum (CC) between MMT patients (n=13), former heroin addicts (n=11) in prolonged abstinence (PA), and healthy control subjects (n=15) using diffusion tensor imaging (DTI). ⋯ Compared with the PA, the MMT subjects had a significantly increased ADC value in the bilateral splenium of CC. Importantly, the methadone dosage used in the MMT group was correlated with the FA value in the left splenium of CC and in the right frontal lobe. Our preliminary results suggest that methadone plays a role in the impairment of WM integrity in heroin users on long-term MMT and the normalization of WM injury may occur during abstinence.
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Neuroscience letters · Apr 2011
Comparative StudyP2RX7 polymorphisms Gln460Arg and His155Tyr are not associated with major depressive disorder or remission after SSRI or ECT.
Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) gene polymorphism, has been suggested to be associated with major depressive disorder (MDD). The association between P2RX7 gene polymorphism and remission after serotonin selective reuptake inhibitors (SSRI) or electroconvulsive therapy (ECT) has not previously been studied. The aims of the present study were to test for an association between P2RX7 polymorphisms Gln460Arg (rs2230912) and His155Tyr (rs208294) and MDD in two patient populations compared to controls. ⋯ There were no differences in allele or genotype frequencies of either rs2230912 or rs208294 between patient groups and controls. Neither rs2230912 nor rs208294 was associated with MDD or remission after SSRI or ECT. The results suggest that P2RX7 gene polymorphisms Gln460Arg (rs2230912) and His155Tyr (rs208294) are not associated with MDD or remission after SSRI or ECT.