Is smoking linked to positive symptoms in acutely ill psychiatric patients?

BACKGROUND: The self-medication hypothesis is commonly put forward to explain the high prevalence of smoking in psychiatric patients. However, studies supporting the self-medication hypothesis have most often been carried out on chronic patients stabilized by antipsychotics. AIM: Given that antipsychotics tend to erase psychiatric symptoms, the present study was undertaken on acutely ill patients usually receiving no medications, or on whom medications are ineffective. METHODS: Participants were 492 consecutively hospitalized patients. They were evaluated the day of their hospitalization with the Brief Psychiatric Rating Scale (BPRS, 18 items). Urinary cotinine and creatinine were measured the morning following their hospitalization. The urinary cotinine/creatinine ratio and the cotinine/creatinine/number of cigarettes smoked per day ratio (nicotine extraction index) were calculated for each patient. RESULTS: The positive symptoms subscale of the BPRS significantly correlated with smoking, whereas other BPRS subscales did not. In patients with mood disorder, the nicotine extraction index correlated with the positive symptoms, activation and hostility subscales, but not with the negative symptoms subscale. Analyses of individual BPRS items using the cotinine/creatinine ratio measure showed that smoking is positively associated with "unusual thought content" and "grandiosity" items and negatively associated with "guilt feeling", "depressed mood" and "motor retardation". Analyses of individual BPRS items using the nicotine extraction index showed a positive association only with "unusual thought content" and "grandiosity" items. Patients with schizophrenia extract more nicotine from cigarettes than other patients. CONCLUSION: In acutely ill psychiatric patients, smoking is linked with positive symptoms and not with negative symptoms.

Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons.

It has been suggested that the beta-carbolines harmane and norharmane may be involved in the pathophysiology of Parkinson's disease, psychosis and addiction, but the mechanisms of these possible effects remain to be elucidated. In the present study, the effects of the two compounds were examined by using in vivo extracellular recordings of ventral tegmental dopamine neurons. The effects of harmane (2mg/kg) and norharmane (2mg/kg), were compared to those of nicotine (11microg/kg), of cotinine (0.5mg/kg), of the monoamine-oxidase-A inhibitor befloxatone (0.12mg/kg), and of the monoamine-oxidase-B inhibitor selegiline (0.5mg/kg). The effects of harmane were also tested after pre-treatment with the nicotine receptor antagonist mecamylamine. The results show that all substances, except befloxatone, activate the firing and/or burst activity of dopamine neurons. The increase in firing rate produced by harmane was approximately 18 times greater than that produced by nicotine. Such powerful excitation of dopamine neurons by harmane may in part explain its involvement in neurotoxicity, psychosis and addiction. The absence of effect of befloxatone supports the hypothesis that the effect of harmane is not related to its monoamine-oxidase-A inhibitory properties. Mecamylamine inhibited by approximately 80% the activity of harmane, indicating that the activating effect of harmane on dopamine neurons involves several mechanisms, among which activation of nicotinic receptors likely has a prominent importance. The results of the present study support the hypothesis that harmane could be a tobacco (or smoke) component other than nicotine involved in tobacco dependence.

Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

Effects of tobacco and cigarette smoke extracts on serotonergic raphe neurons in the rat.

Tobacco components other than nicotine might participate in the behavioural effects of smoking. In this study, in-vivo recordings of serotonergic dorsal raphe neurons were performed in the anesthetized rat, whereas tobacco extracts, cigarette smoke extracts, nicotine, nornicotine or anabasine were intravenously injected. All substances inhibited the neurons, and all inhibitions were completely blocked by the nicotine receptor antagonist mecamylamine. The effects of the extracts were much more potent than those of individual substances. These results support the hypothesis that the acute inhibition of serotonin neurons by tobacco compounds is completely related to an effect on nicotine receptors. Tobacco extracts and tobacco smoke extracts may be useful tools for the study of the effects of central effects of smoking.

Harmane inhibits serotonergic dorsal raphe neurons in the rat.

RATIONALE: Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively. OBJECTIVES: To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested. METHODS: In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat. RESULTS: Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane. CONCLUSIONS: Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.