Abstract
Nicotine causes tobacco dependence, which may result in fatal respiratory diseases. The striatum is a key structure of forebrain basal nuclei associated with nicotine dependence. In the striatum, glutamate release is increased when α7 nicotinic acetylcholine receptors expressed in the glutamatergic terminals are exposed to nicotine, and over-stimulates glutamate receptors in gamma amino-butyric acid (GABA)ergic neurons. These receptor over-stimulations in turn potentiate GABAergic outputs to forebrain basal nuclei and contribute to the increase in psychomotor behaviors associated with nicotine dependence. In parallel with glutamate increases, nicotine exposure elevates brain-derived neurotrophic factor (BDNF) release through anterograde and retrograde targeting of the synapses of glutamatergic terminals and GABAergic neurons. This article reviews nicotine-exposure induced elevations of glutamatergic neurotransmission, the bidirectional targeting of BDNF in the striatum, and the potential regulatory role played by BDNF in behavioral responses to nicotine exposure.
Highlights
Nicotine is a major constituent of the tobacco plant and commercial cigarettes, and is considered to be the cause of compulsive tobacco smoking [1,2]
Nicotine delivered to the striatum increases extracellular dopamine and glutamate concentrations by stimulating nicotinic acetylcholine receptors [3,4,5,6]
Systemic repeated exposure to nicotine dose-dependently increases dopamine levels in the caudate nucleus and putamen (CPu) and nucleus accumbens (NAc) [29], and that local infusion of nicotine increases glutamate release in the striatum [6,30]. These findings suggest that nicotine administration potentiates glutamate release in the GABAergic neurons of the striatum by integrating dopaminergic neurotransmission
Summary
Nicotine is a major constituent of the tobacco plant and commercial cigarettes, and is considered to be the cause of compulsive tobacco smoking [1,2]. Resulting elevated glutamate levels stimulate ionotropic- and metabotropic glutamate receptors (iGluRs and mGluRs) expressed in striatal gamma amino-butyric acid (GABA)ergic neurons [10,11,12]. These stimulations cause short- and long-term changes in neuronal activities and gene expressions and cause behavioral changes by upregulating GABAergic outputs to other parts of basal ganglia [7,13,14]. Nicotine exposure upregulates expression of brain-derived neurotrophic factor (BDNF) in glutamatergic terminals and GABAergic neurons of the striatum [15,16,17]. This study was undertaken to review spatiotemporal interactions of glutamate and BDNF in the striatum that modulate psychomotor and nicotine-seeking behaviors in response to nicotine exposure
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