Efeitos da modulação nicotínica sobre a neuroplasticidade glutamatérgica em humanos
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Universidade Federal do Espírito Santo
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Nicotine (NIC) alters cognitive functions by modulating neuroplasticity and cortical excitability in animals and humans. It was recently shown that NIC can not only stabilize, but also disrupt formation of glutamatergic plasticity in the human cerebral cortex. The impact of NIC on plasticity is thought to be primarily determined via calcium channel properties of nicotinic receptor subtypes, and glutamatergic plasticity is likewise calcium-dependent. Therefore glutamatergic plasticity is likely modulated by the impact of nicotinic receptor-dependent neuronal calcium influx. We tested this hypothesis for transcranial direct current stimulation (tDCS) -induced long-term potentiation-like plasticity, which is abolished by nicotine in healthy nonsmokers, possibly due to calcium overflow. To reduce calcium influx under NIC, we blocked NMDA receptors, which have calcium channel properties. We hypothesized that NMDA receptor block alone will prevent tDCS-induced plasticity, but should reestablish it under nicotine due to reduction of calcium influx. We applied anodal tDCS in 13 healthy non-smokers combined with 15 mg nicotine patches and the NMDA receptor antagonist dextromethorphan (DMO) in three different doses (50, 100 and 150 mg) or placebo medication. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation (TMS)-induced motor evoked potential (MEP) amplitudes for up to 36 h after plasticity induction. NIC abolished the anodal tDCS-induced motor cortex excitability enhancement, which was however restituted under the medium dosage of DMO. In contrast, low-dosage DMO did not affect the impact of nicotine on tDCS-induced plasticity and high-dosage DMO abolished plasticity. For DMO alone, the low dosage had no effect, but medium and high dosages abolished tDCS-induced plasticity. These results enhance our knowledge about the proposed calcium-dependent impact of nicotine on plasticity and might be relevant for the development of novel nicotinic treatments for cognitive dysfunction., dextromethorphan, neuroplasticity, nicotine, nicotinic receptors, transcranial direct current stimulation, dextrometorfano, estimulação transcraniana por corrente contínua, neuroplasticidade, nicotina, receptores nicotínicos
Citação
LUGON, Marcelo Di Marcello Valladão. Efeitos da modulação nicotínica sobre a neuroplasticidade glutamatérgica em humanos. 2015. Tese (Doutorado em Ciências Fisiológicas) - Universidade Federal do Espírito Santo, Centro de Ciências da Saúde, Vitória, 2015.