Exploiting Nicotinic Receptor Mechanisms for the Treatment of Schizophrenia and Depression

Abstract

Smoking rates are higher in persons with schizophrenia (SZ; 58%–88%) and major depressive disorder (MDD; 40%–60%) compared to the U.S. general population (∼23%). Nicotinic acetylcholine receptors (nAChRs) are the brain receptors for nicotine. SZ and MDD are nicotine-responsive neuropsychiatric disorders. Thus, it is hypothesized that the higher rates of smoking in the SZ and MDD populations can be attributed to the pathophysiology of these disorders. Knowledge of nAChR functioning can be exploited in therapeutics for treating both the addiction and clinical aspects of these disorders. This article reviews the neurobiology of nAChR and biological dysregulation inherent in SZ and MDD. In addition, manipulation of nAChRs with appropriate agonists and antagonists is discussed. Specifically, nAChRs can be stimulated to improve cognitive deficits associated with SZ and blocked for the treatment of selective serotonin reuptake inhibitor–refractory major depression; a combination of agonism and antagonism may assist with smoking cessation in SZ populations. This knowledge has significant implications for further development of pharmacotherapies for treatment of SZ and MDD symptoms and for smoking cessation in these disorders.

KEYWORDS:

• Schizophrenia
• depression
• cigarette smoking
• addiction vulnerability
• nicotinic receptor
• smoking cessation
• therapeutics