Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Nov 2009
Nicotinic activation of laterodorsal tegmental neurons: implications for addiction to nicotine.
Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. ⋯ We also found that direct nicotinic actions on cholinergic LDT neurons were mediated by receptors containing alpha 7, beta2, and non-alpha 7 subunits. These findings led us to suggest that nicotine exposure from smoking will enhance both the excitability and synaptic modulation of cholinergic and non-cholinergic LDT neurons, and increase their signature neurotransmitter outflow to target regions, including the VTA. This may reinforce the direct actions of this drug within reward circuitry and contribute to encoding stimulus saliency.