Nicotinic receptors, stress, and neuroinflammation
Recent data are challenging our traditional view of nicotine as a single-handed harmful drug of addiction with no alternative roles. At the moment, nicotinic ligands appear to be promising candidates for breaking a causal chain connecting stress, inflammation, and neuropsychiatric disease.
Intense or prolonged stress is known as a potential trigger to a large class of psychiatric conditions including schizophrenic psychoses, anxiety spectrum disorders, and depression. Data of the last decade is beginning to recognize inflammation as a factor shared by this apparently inhomogeneous set of illnesses. An abnormally large percentage of patients suffering from neuropsychiatric illness also shares nicotine-(ab)use as common habit, suggestive of an attempt at self-medication. Evidence of the last two decades shows that activation of the anti-inflammatory reflex, mediated by activation of nicotinic receptors on immune cells, decreases the release of pro-inflammatory cytokines.
Neurons releasing g-amino butyric acid (GABA) appear to be exquisitely sensitive to neuro-inflammation associated with different stressors. The anti-inflammatory effects associated with the activation of nicotinic receptors in immune cells may be a crucial factor to decrease detrimental effects of altered cytokine levels in GABAergic central neurons. The pharmacological or electrophysiological activation of nicotinic receptors has unexplored potential for the treatment of such conditions, particularly for patients refractory to traditional illness-specific treatment.