Int Rev Neurobiol
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Methamphetamine (MAP), a drug of abuse known worldwide for its addictive effects and neurotoxicity, causes somatic and psychiatric disorders. MAP enters terminals/neurons via monoamine transporters, displaces both vesicular and intracellular monoamines, and facilitates the release of monoamines into the extraneuronal space through synaptic transport via the monoamine transporters. Chronic psychostimulant abusers exhibit psychotic features, including delusions and auditory hallucinations. ⋯ The deletion of DAT attenuates the locomotor effects of MAP and may play larger role in behavioral responses to MAP compared to the deletion of VMAT2. MAP produces hyperthermia and/or neuronal toxicity in most species. The effects of MAP in DAT or serotonin transporter (SERT) single knockout (KO) mice and DAT/SERT double KO mice suggested that DAT and SERT are key molecules for hyperthermia and neuronal toxicity of MAP.
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Experimental evidence suggests that reinnervation of the distal stump of a transected nerve may occur if the former is coapted end-to-side to the trunk of an adjacent nerve. Axonal regeneration occurs by collateral sprouting of healthy donor nerve axons, induced by neurotrophic factors. ⋯ End-to-side neurorrhaphy has already been used in the clinical practise, but there are still some issues that have not been completely clarified yet: (i) the origin of regenerating axons, (ii) collateral sprouting molecular mechanisms, and (iii) the degree of donor nerve axotomy needed for motor functional recovery. The results of experimental studies trying to investigate these parameters are briefly discussed in this review article.
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Elucidation of the mechanism of neuropathic pain caused by vincristine is required because long-term treatment with this anticancer agent often causes neuropathic pain. We refer to the involvement of inflammatory mediators in vincristine-induced neuropathic pain in this review. Several reports using rodents have shown that long-lasting neuropathic pain (mechanical allodynia) is caused by repeated systemic injection of vincristine. ⋯ In the CNS, these inflammatory cytokines have an important role in the neuropathic pain caused by vincristine. Immune-modulating agents that prevent activation of immune cells and/or the inhibitory agents of inflammatory cytokines could prevent the neuropathic pain caused by vincristine. These agents could increase the tolerability of vincristine when used for the treatment of leukemia and lymphoma.
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Observational studies in humans suggest that exposure to marijuana and other cannabis-derived drugs produces a wide range of subjective effects on mood tone and emotionality. These observations have their counterpart in animal studies, showing that cannabinoid agonists strongly affect emotional reactivity in directions that vary depending on dose and context. Based on these evidence, the activation of central CB(1) receptor has emerged as potential target for the development of antianxiety and antidepressant therapies. ⋯ Therefore, inhibition of AEA metabolism activity could amplify CB(1) activation mainly where AEA release is higher. Furthermore, the inhibition of FAAH causes an accumulation of AEA but not 2-AG, which, being 200-fold more abundant than AEA in the brain, might differently modulate CB(1)-mediated behavioral responses. The evidence outlined above supports the hypothesis that the EC system plays an important role in anxiety and mood disorders and suggests that modulation of FAAH activity might be a pharmacological target for novel anxiolytic and antidepressant therapies.