Nicotinic receptor dysfunction is common across many mental illnesses[5, 6]. Nicotine activates nicotinic acetylcholine receptors in the same way as the endogenous neurotransmitter acetylcholine. Rates of smoking are significantly higher amongst depressed, anxious, and schizophrenic individuals compared to the general population[7], suggesting individuals may be “self-medicating” to alleviate some of their symptoms. In support of this possibility, nicotine has anxiolytic actions in humans[7], and nicotine also ameliorates sensory gating attentional deficits in schizophrenia patients[8]. There are several nicotinic receptor subtypes, and the two most widely found in the brain and implicated in psychiatric disorders are the high affinity nicotinic alpha4 beta2 receptors and the low affinity nicotinic alpha7 receptors[9]. Animal studies demonstrate that alpha7 or alpha4 beta2 nicotinic receptor activation facilitates memory performance in a variety of testing paradigms[10, 11]. There is also evidence to suggest that disrupting the balance of hippocampal alpha7 and alpha4 beta2 receptor activity alters memory function in rats[10, 11]. In addition, both alpha7 and alpha4 beta2 hippocampal receptors have been shown to influence anxiety and depressive-like behaviors in rodents[12]. Taken together, these data suggest that alpha7 and alpha4 beta2 nicotinic receptors in the hippocampus play a key role in both cognitive and affective behavioral function.
Representative coronal section depicting a-BTX binding in the hippocampus of a rat. a-BTX selectively binds to alpha7 nAChRs, allowing for quantification of alpha7 receptors in the brain.
Representative coronal section depicting epibatadine binding in the hippocampus of a rat. Epibatadine selectively binds to alpha4 beta2 nAChRs, allowing for quantification of these receptors in the brain.