ABSTRACT
The impact of nicotine (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 NIC in nonsmokers. To reduce calcium influx under NIC, we blocked N-methyl-d-aspartate (NMDA) receptors. We applied anodal tDCS combined with 15 mg NIC patches and the NMDA-receptor antagonist dextromethorphan (DMO) in 3 different doses (50, 100, and 150 mg) or placebo medication. Corticospinal excitability was monitored by single-pulse transcranial magnetic stimulation-induced motor-evoked potential amplitudes after plasticity induction. NIC abolished anodal tDCS-induced motor cortex excitability enhancement, which was restituted under medium dosage of DMO. Low-dosage DMO did not affect the impact of NIC 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 NIC on plasticity in humans and might be relevant for the development of novel nicotinic treatments for cognitive dysfunction.
Subject(s)
Dextromethorphan/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Neuronal Plasticity/drug effects , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Transcranial Direct Current Stimulation , Adult , Analysis of Variance , Dose-Response Relationship, Drug , Evoked Potentials, Motor/drug effects , Evoked Potentials, Motor/physiology , Female , Humans , Male , Motor Cortex/drug effects , Motor Cortex/physiology , Neuronal Plasticity/physiology , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Time FactorsABSTRACT
BACKGROUND: Extensive evidence supports the notion that modulation of PFC excitability using low-intensity electrical stimulation is a promising modality for treating neuropsychiatric diseases and improving cognitive function. OBJECTIVE: This study examined the effects of epidural direct current stimulation (eDCS), a method providing smaller shunting of current and more focal stimulation, on spatial working memory. METHODS: Male Wistar rats that were well trained in an 8-arm radial maze and in which 5-mm round electrodes were implanted over the left medial prefrontal cortex (mPFC) received anodal eDCS (400 µA during 11 min) (n = 9) or sham procedure (n = 9) five minutes before delayed tests in the radial maze. RESULTS: Animals that received eDCS over the left mPFC had significantly fewer errors in the post-delay performance on the 1-h (P < 0.01), 4-h (P < 0.001), and 10-h (P < 0.001) delayed tests compared with sham-treated animals. General locomotor activity was unaffected because time spent in each visited arm did not change significantly by eDCS. There was no evidence of neuronal lesions in the mPFC underneath the eDCS. CONCLUSIONS: Our results suggest that epidural direct current stimulation over the mPFC facilitates spatial working memory in rats, an effect that persisted over the long term.
