Background: The hypothalamus harbors high levels of cholinergic neurons and axon
terminals. Nicotinic acetylcholine receptors, which play an important role in cholinergic neurotransmission,
are expressed abundantly in the hypothalamus. Accumulating evidence reveals a regulatory
role for nicotine in the regulation of the stress responses. The present review will discuss the
hypothalamic neuropeptides and their interaction with the nicotinic cholinergic system. The anatomical
distribution of the cholinergic neurons, axon terminals and nicotinic receptors in discrete
hypothalamic nuclei will be described. The effect of nicotinic cholinergic neurotransmission and
nicotine exposure on hypothalamic-pituitaryadrenal (HPA) axis regulation at the hypothalamic level
will be analyzed in view of the different neuropeptides involved.
Methods: Published research related to nicotinic cholinergic regulation of the HPA axis activity at
the hypothalamic level is reviewed.
Results: The nicotinic cholinergic system is one of the major modulators of the HPA axis activity.
There is substantial evidence supporting the regulation of hypothalamic neuropeptides by nicotinic
acetylcholine receptors. However, most of the studies showing the nicotinic regulation of hypothalamic
neuropeptides have employed systemic administration of nicotine. Additionally, we know
little about the nicotinic receptor distribution on neuropeptide-synthesizing neurons in the hypothalamus
and the physiological responses they trigger in these neurons.
Conclusion: Disturbed functioning of the HPA axis and hypothalamic neuropeptides results in pathologies
such as depression, anxiety disorders and obesity, which are common and significant
health problems. A better understanding of the nicotinic regulation of hypothalamic neuropeptides
will aid in drug development and provide means to cope with these diseases. Considering that nicotine
is also an abused substance, a better understanding of the role of the nicotinic cholinergic system
on the HPA axis will aid in developing improved therapeutic strategies for smoking cessation.