Nicotine has been proposed to provide anxiety relief, oral gratification and self-medication of psychotic symptoms in psychiatric patients. In order to investigate the relations between psychopathology and tobacco use we measured the concentration of cotinine, the major metabolite of nicotine, in the saliva of psychiatric patients and healthy volunteers. In a sample of 42 schizophrenic patients we correlated smoking status, cotinine levels, symptom profiles (PANSS), and neuroleptic side effects (Simpson-Angus). Despite reporting the same amount of cigarettes consumed per day the saliva concentration of cotinine was significantly higher in patients with schizophrenia than in the controls. There were no significant differences in clinical characteristics between smoking and non-smoking schizophrenic patients, but smokers tended to be on higher drug doses. High cotinine concentrations correlated significantly with the negative symptoms Passive withdrawal and Social avoidance. The results indicate that the schizophrenic patients smoke cigarettes more intensely than other patients and healthy subjects. The correlation between high cotinine levels and negative symptomatology may reflect an attempt by schizophrenic patients to overcome the emotional withdrawal and thus the results may lend support to a self-medication hypothesis.

(S)- and (R)-[11C]nicotine were synthesized by methylation of (S)- and (R)-nornicotine using [11C]methyl iodide. Following their intravenous injection in tracer doses to smoking and nonsmoking healthy males the radioactivity in arterial blood showed a sharp peak at about 1 min followed by a plateau level for the remaining 50 min of recording. Uptake in the brain, as measured by positron emission tomography (PET), was rapid with a peak at 5 min followed by a steady decline towards the end of the measurement. The regional distribution of radioactivity followed essentially the distribution of gray matter with high uptake in the cortex, the thalamus and the basal ganglia and low uptake in the pons, cerebellum and white matter. Levels of the labelled natural enantiomer, (S)-[11C]nicotine, were higher than those of the synthetic enantiomer, (R)-[11C]nicotine, particularly in the smokers. The time-activity curves of (S)-[11C]nicotine uptake were not changed by co-administration of 1.0 mg of unlabelled nicotine with the labelled nicotine. Similarly administration of unlabelled nicotine at the peak of radioactivity, 6 min following (S)-[11C]nicotine, had no effect on the time-activity curves. Thus essential criteria for visualizing receptor binding with the PET technique could not be fulfilled. Calculation of kinetic constants using a two-compartment model gave values indicating that the brain uptake of [11C]nicotine is mainly determined by the cerebral blood flow, extraction of the tracer over the blood-brain barrier and unspecific binding. Thus 11C-labelled nicotine does not seem to be a suitable tracer for PET studies of nicotinic cholinergic receptors in the human brain.

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