Nicotinic cholinergic control

Until recently, little attention had been paid to nicotinic mechanisms in explaining either the pathophysiology or treatment of AD. Patients with AD have a marked reduction in cortical nicotinic cholinergic receptor binding compared with that of age-matched control subjects (Aubert et al. 1992 Flynn and Mash 1986 Whitehouse et al. 1986). Psychiatrically healthy elderly subjects show an age-related decline in cortical nicotinic binding (Flynn and Mash 1986). 

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Cocaine use has been associated with a reduced inhibitory response of the P50 auditory evoked response, attributed to increased catecholaminergic and reduced cholinergic neurotransmission secondary to cocaine (127). In a double-blind, placebo-controlled study, 11 cocaine users in the first and third weeks of detoxification had electrophysiological testing 10 minutes before and 30 minutes after taking nicotine gum 6 mg. Nicotine briefly reversed the inhibitory deficit. 

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