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6. Nicotine and Specific Diseases

There is considerable evidence that tobacco smoking and depression are linked. The prevalence of smoking among schizophrenic patients is much higher than in patients with other psychiatric disorders and much higher than in normal populations (Lohr & Flynn, 1992). Sustained nicotine administration has found to improve learning in patients with Alzheimer’s disease (Wilson et al., 1995). Epidemiological studies have demonstrated an inverse relationship between smoking and the development of Parkinson’s disease (Le Houezec, 1998). Gilles de la Tourette’s syndrome is a genetic disorder whose symptoms showed sustained improvement after acute administration of nicotine (Le Houezec, 1998)

Smoking is more prevalent in depression and smoking cessation is less successful in depressed patients (Fowler, Volkow, Wang, Pappas, Logan, Shea, et al., 1996). Of nicotine-dependent smokers, 26.7% had a history of major depression; of nondependent smokers, 12% had a history of major depression; and of non-smokers 9.4% had a history of major depression (Le Houezec, 1998). Dopaminergic depletion is involved at least in some aspects of major depression. The effects of smoking and depression are better understood when the effects of nicotine are assessed apart from the effects of other constituents of smoke.

Tobacco smoke exposure, but not nicotine administration, is associated with marked reduction in MAO A and MAO B, which are essential metabolic enzymes for many neurotransmitters (Bergen & Caporaso, 1999). Studies in animals have reported that the simultaneous inhibition of both MAO subtypes produces large increases in serotonin (Fowler, et al, 1996). Both MAO A and B break down dopamine and their simultaneous inhibition by smoke may combine to enhance brain dopamine which has been implicated in reward and reinforcement. Nicotine stimulates dopamine release and an elevation in dopamine in the nucleus accumbens is associated with reinforcement (Fowler, Volkow, Wang, Pappas, Logan, MacGregor, et al., 1996). There may be a synergistic effect of MAO B inhibition by cigarette smoke to enhance nicotine induced dopaminergic neurotransmission (Fowler et al., 1998).

Around 90% of people with schizophrenia smoke; this is approximately twice the prevalence as people with other psychiatric disorders and three times as prevalent as the general population (Le Houevec, 1998). People with schizophrenia are more likely to be heavy smokers with 58.5% smoking high tar cigarettes compared to only 0.9% of the general population (Lohr & Flynn, 1992). Patients with schizophrenia often smoke down to the filter where the highest concentration of nicotine occurs. Schizophrenics are also more likely to have smoked for extensive periods of time.

The psychostimulant effects of nicotine might help the schizophrenic compensate for their cognitive deficits, particularly attentional processes (Le Houevec, 1998). It has also been hypothesized that nicotine could normalize some of the neuronal deficits involved in schizophrenia. Adler, Hoffer, Wiser, and Freedman (1993) showed an impairment of sensory gating and found that smoking restored the impaired auditory information processing observed in people with schizophrenia who smoke.

Nicotine’s effect on mood may help people with schizophrenia cope with anhedonia or more generally to ameliorate negative symptoms, such as apathy and lack of motivation which may be related to the hypoactivity of the dopaminergic reward system (Le Houevec, 1998). By stimulating the release of mesolimbic dopamine, nicotine may counteract negative symptoms. Nicotine may also lessen the side effects of neuroleptics (antiparkinsonian effects).

Patients with Alzheimer’s disease have large reductions of nicotinic receptors in both neocortex and hippocampus compared with healthy people (Le Houevec, 1998). Because nicotine has a positive effect on cognitive functioning in people without Alzheimer’s disease, nicotinic receptors may contribute to normal cognitive functioning.

Patients who had Alzheimer’s disease who were administered nicotine subcutaneously showed improved sustained visual-attention response time and perceptual performance in proportion to dose. Memory, behavior, and global cognition were not significantly affected (Wilson et al., 1995). Nicotinic receptor stimulation may also protect neurons against beta-amyloid toxicity, which may provide neuroprotection in the neurodegenerative process of Alzheimer’s disease.

Smokers are half as likely to have Parkinson’s disease as nonsmokers

(Le Houevec, 1998). In Parkinson’s disease there is a deficit in dopaminergic function. Nicotine stimulates dopamine release in striatal structures and in the substantia nigra; chronic nicotine administration increases motor stimulation.

Cigarette smoking has a beneficial effect on parkinsonian symptoms (Nishmura, Tachibana, Okuda, & Sugita, 1997). It has been suggested that the desensitization of dopaminergic neurons by nicotine may reduce Ca++ injury during acute lesions and consequently the extent of cell damage or death. Nicotine has also been found to reduce tremors in Parkinson’s disease (Le Houevec, 1998).

Tourette’s syndrome is a genetic disorder thought to result from a basal ganglia abnormality (Le Houezec, 1998). The pathophysiological basis of Tourette’s syndrome may be an imbalance between cholinergic and dopaminergic activity within the striatum. Nicotine may act pharmacologically by restoring the cholinergic-dopaminergic balance by acting on nicotinic receptors, which in turn increase the activity of the GABAergic efferent striatal pathway on motor behavior. In a study (Sanberg et al., 1997) clinical Tourette’s symptoms improved with nicotine therapy and effects persisted between 8 and 16 weeks after one dose(acute) or 6 days (subchronic) of nicotine administration.

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