Modulation of dopamine release in the striatum by physiologically relevant levels of nicotine

Abstract

Striatal dopamine (DA) release can be independently triggered not only by action potentials (APs) in dopaminergic axons but also APs in cholinergic interneurons (ChIs). Nicotine causes addiction by modulating DA release, but with paradoxical findings. Here, we investigate how physiologically relevant levels of nicotine modulate striatal DA release. The optogenetic stimulation of ChIs elicits DA release, which is potently inhibited by nicotine with an IC 50 of 28 nM in the dorsal striatum slice. This ChI-driven DA release is predominantly mediated by a6b2* nAChRs. Local electrical stimulus (Estim) activates both dopaminergic axons and ChIs. Nicotine does not affect the AP DA -dependent DA release (AP DA , AP of dopaminergic axon). During burst Estim, nicotine permits the facilitation of DA release by prevention of DA depletion. Our work indicates that cholinergic stimulation-induced DA release is profoundly modulated by physiologically relevant levels of nicotine and resolves the paradoxical observation of nicotine's effects on striatal DA release.

Dopamine release from transplanted neural stem cells in Parkinsonian rat striatum in vivo

“…The pcCFE was placed in the striatum, and DA release was evoked by perfusion of 70 mM K + through the drug-delivery tube. DA recording of striatal slices was performed as previously described (49). DA overflow was evoked by perfusion with 70 mM K + for 10 s and recorded by CFE.…”

“…Immunohistochemistry was performed as previously described (49,50), with slight modifications. Briefly, rats were anesthetized and prefixed with 4% (wt/vol) paraformaldehyde through transcardial perfusion.…”

Frequency-Dependent Modulation of Dopamine Release by Nicotine and Dopamine D1 Receptor Ligands: An In Vitro Fast Cyclic Voltammetry Study in Rat Striatum

“…Activation of cholinergic interneurons (ChI) by flashes of light caused dopamine release via activation of nicotinic receptors on dopamine axons. More recently, Wang and co-workers showed that nicotine could reduce the ChI-induced depletion of the dopamine vesicular pool by suppressing the ChI pathway and that following suppression of this pathway nicotine can facilitate dopamine release during sustained burst local field electrical stimulation in the striatum, suggesting an important role for ChI [9]. Dopamine transmission in the brain utilizes an auto-regulatory system by which dopamine D2-like receptor (D2R) activation will inhibit the further release of dopamine and modulate uptake into the pre-synaptic cell.…”

Nicotine Replacement Therapy

“…It has stimulant properties and enhances rewarding effects by increasing downstream release of dopamine in the ventral tegmentum of the midbrain (10). Additionally, nicotine's desensitization of a6b2 nAChRs on cholinergic interneurons of the striatum slows dopamine depletion and enhances the contrast between dopamine release evoked by phasic and tonic firing of dopaminergic nerves in the striatum, leading to increased reward salience (11). Both positive reinforcement (e.g., heightened vigilance, improved mood, and weight loss) and negative reinforcement (alleviation of withdrawal symptoms, e.g., anxiety, irritability, impaired concentration, and increased appetite) mediate nicotine addiction (12).…”