Effects of Nicotine on Brain and Behavior: How nAChRs Modulate Circuits Related to Mood and Aggression
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Acetylcholine signaling influences behaviors related to diverse functions, including drug abuse, attention, food intake, and mood. The ability of acetylcholine to coordinate the response of neuronal networks in many brain areas makes cholinergic modulation an essential mechanism underlying complex behaviors. Interestingly, increasing acetylcholine signaling using pharmacological or genetic methods can induce symptoms related to anxiety and depression in humans and in rodent models. Studies of anxiety- and depression-like behaviors in mice have identified specific cholinergic receptors and brain areas that are necessary for ACh effects. In addition, mouse studies have identified interactions between ACh and monoamine neurotransmitters that are targeted by most antidepressant medications that are effective in human patients. These studies suggest that abnormalities in the cholinergic system may be critical for the etiology of mood disorders and could represent a novel endophenotype of depression that could be targeted to develop novel antidepressant medications. Thus, ACh signaling could contribute to the balance between adaptive responses to stress and mood disorders.