The question that remains

is how blockade of these ligand-gated channels could account for a beneficial outcome on the depressive status of the patients. The use of a broad-spectrum blocker of the nicotinic receptors, mecamylamine, which is devoid of action on monoamine reuptake, may provide a first indication, especially since it was found to have a beneficial effect in the treatment of depression.42,43 The Inhibitors,research,lifescience,medical hypothesis is that depression is accompanied by hypercholinergic activity.42,43 Nicotinic receptors and the HPA axis Mood disorders, which include depression, are often thought of as a dysfunction or imbalance of the hypothalamic-pituitary-adrenal (HPA) system. The two major contributions with opposing modulation of the HPA Inhibitors,research,lifescience,medical are the amygdala, with a positive action, and the hippocampus, with a negative feedback. We should therefore consider three features of the nicotinic receptors in the HPA system: The high level and diversity of neuronal

nicotinic receptor expression in both hippocampus27,28 and amygdala.44 The importance of nAChRs in the hypothalamus circuits.45 The fact that steroids and mineralocorticoids modulate the nAChRs function.46-48 While both amygdala and hippocampus have a large number of nicotinic receptors, more Inhibitors,research,lifescience,medical attention was paid to studies of nicotinic receptor function in the hippocampus.31,49 However, given the complexity of hippocampal circuits and the multiple effects of acute and chronic nicotine exposure, the main outcome of nAChR stimulation remains to be elucidated. Despite our incomplete understanding of nicotine’s action on Inhibitors,research,lifescience,medical the amygdala and hippocampus circuitry, there is no doubt that exposure to this agent will alter the network activity and may cause an imbalance Inhibitors,research,lifescience,medical of the HPA. Histological analysis of the hypothalamus revealed that this brain area has a high level of nAChR expression.28

Moreover, the functionality of these receptors in the paraventricular nucleus has been demonstrated by electrophysiology.50 Parvocellular and magnocellular neurons that project to the anterior and posterior areas of the pituitary, respectively, have been shown to respond to ACh or nicotine.50 In an attempt to study effects of nicotine withdrawal in an animal model, rats were implanted with minipumps dispensing nicotine. Dichloromethane dehalogenase HPA activity was determined on the second day after withdrawal of nicotine using the stress-induced corticosterone response and the dexamethasone suppression test.51 The results obtained by these authors suggest that the lower sensitivity of the HPA axis to stress during nicotine with-drawal may trigger depression during smoking cessation, but this website glucocorticoid receptor and corticotropin-releasing hormone do not appear to play a significant role in the condition tested.