Matts Eriksson

Is long-term heavy alcohol consumption toxic for brain serotonergic neurons? Relationship between years of excessive alcohol consumption and serotonergic neurotransmission

The relationship between years of excessive alcohol consumption and central serotonergic neurotransmission, as assessed by the prolactin (PRL) response to D-fenfluramine, was investigated in 22 male alcohol-dependent subjects. A negative correlation was obtained, that is, the longer duration of excessive alcohol consumption the lower PRL response to D-fenfluramine. It is therefore suggested that long duration of excessive alcohol consumption in alcohol-dependent subjects causes a reduction in central serotonergic neurotransmission, possibly by a toxic effect of alcohol on serotonin neurons. The relationship between depressive and anxiety symptoms during on-going drinking and the PRL response to D-fenfluramine was also investigated. No such correlations were obtained, suggesting that reduction in central serotonergic neurotransmission does not pre-dispose to the development of depressive and anxiety symptoms, at least in relation to on-going drinking in alcohol-dependent subjects.

Personality profile in type I alcoholism: long duration of alcohol intake and low serotonergic activity are predictive factors of anxiety proneness

Summary.The aim of the present study was to further investigate personality profiles in male type I alcohol-dependent subjects (n = 33), in relation to central serotonergic neurotransmission, history of excessive alcohol consumption and present use of tobacco. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to D-fenfluramine. By using the Temperament and Character Inventory and the Karolinska Scales of Personality, all subjects self-rated their personality profile. The results showed that individuals with low PRL response and long duration of excessive alcohol consumption had significantly higher anxiety proneness, and that years of excessive alcohol consumption was the strongest predictor. Long duration of excessive alcohol consumption thus appears to have an influence on personality traits in male type I alcohol-dependent individuals and these personality traits may therefore be a consequence of, rather than preceding, alcoholism in these individuals.

Relationship between central serotonergic neurotransmission and reduction in alcohol intake by citalopram

The relationship between the effect of citalopram on alcohol intake and central serotonergic neurotransmission, as assessed by prolactin (PRL) response to fenfluramine, was investigated in 17 male heavy drinkers. A positive correlation was obtained, suggesting that the status of central serotonergic neurotransmission in individuals is associated with the treatment response to citalopram. When the group of subjects were divided into those with high and low PRL response (above and below median, respectively) to fenfluramine, those with high PRL response had a significant reduction in alcohol intake during citalopram treatment, whereas those with low PRL response had no such effect. Thus, in subjects with evidence of unimpaired or only slightly impaired central serotonergic neurotransmission (high PRL response) citalopram may have beneficial effect on alcohol consumption, whereas in those with more evidently impaired serotonergic neurotransmission (low PRL response) citalopram treatment may have no effect on or may even increase the alcohol consumption.

Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake.

In an open study, 14 alcohol-dependent male patients were treated with the selective serotonin reuptake inhibitor (SSRI) Zimelidine, 200 mg daily, for six months. They were given psychosocial therapy before and during the study. The number of days of alcohol intake was statistically significantly reduced from a mean of 14 days per month before to 1-5 days during drug treatment. No effect was observed on the amount of daily alcohol intake on drinking days. No tolerance to the effect of Zimelidine was observed during the study. The findings suggest an effect of combined psychosocial support with SSRI treatment that seems to be of clinical significance.

No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: a pilot study

Two bases for this study were the theory of stress as a provoking factor for high alcohol consumption in human being and findings that the stress hormones stimulate ethanol intake in rats. We therefore investigated whether the cortisol-synthesis inhibitor metyrapone could reduce high alcohol consumption in socially stable subjects who reported drinking mainly for relaxation purposes. Most of the investigated subjects were found to be alcohol dependent (81%), with moderately high levels of intake, yet they had not reported more severe life problems. All subjects reported their daily alcohol consumption during 2-week baseline, medication, and postmedication periods. Sixteen subjects were given 1 g of metyrapone orally daily for 14 days, and 15 subjects received placebo. Morning serum cortisol concentration was assessed four times in the course of the study period. Metyrapone treatment was not found to reduce alcohol consumption more than placebo. Serum cortisol concentrations remained within the laboratory reference interval during the study and did not differ between the study groups. In this study, we found that a cortisol-synthesis inhibitor had no effect on alcohol consumption. One reason may be that cortisol secretion has no role in the maintenance of high alcohol consumption. On the other hand, because this study is the first of its kind, further studies using other doses of treatment and treatment schedules are suggested.

Tobacco Use is Associated With Reduced Central Serotonergic Neurotransmission in Type 1 Alcohol‐Dependent Individuals

BACKGROUND Reduced central serotonergic neurotransmission in alcohol dependence may be attributed to the effects of cigarette smoking (and possibly more specifically to nicotine) rather than to alcoholism or its subtypes. The aim of the present study was therefore to compare central serotonergic neurotransmission in tobacco-using (cigarette smokers and users of smokeless tobacco, i.e., snuffers) alcohol-dependent individuals to that of tobacco-nonusing alcohol-dependent individuals. METHODS The central serotonergic neurotransmission was assessed by the prolactin (PRL) response to the serotonin-releasing agent D-fenfluramine (30 mg orally). Male subjects (n = 37) aged 20-65 years were recruited for this purpose. They were all type 1 alcohol-dependent individuals and had ended their alcohol intake the day before the D-fenfluramine challenge test. RESULTS There was no difference in baseline PRL concentrations between tobacco-using (n = 18) and tobacco-nonusing (n = 19) alcohol-dependent individuals. On the other hand, the maximum PRL response after D-fenfluramine was significantly lower in the tobacco-using group as compared to the tobacco-nonusing individuals. CONCLUSION Whether the reduction in central serotonergic neurotransmission in tobacco-using alcohol-dependent individuals is pre-existing or a result of tobacco use remains to be elucidated.

Platelet monoamine oxidase B (MAO-B) activity and its relationship to DL-fenfluramine-induced prolactin response in healthy men

Summary.Several techniques are used to assess central serotonergic neurotransmission in man, e.g. challenge tests (hormonal and physiological responses to serotonin active drugs), platelet MAO-B activity as well as brain imaging techniques. Little is known about how these tests relate to each other. The aim of the present study was therefore to investigate if platelet MAO-B activity could be related to hormonal and temperature responses to the serotonin active drug DL-fenfluramine in healthy men. Twelve male subjects without any history of psychiatric disorders or drug abuse/dependencies were recruited. Prior to the challenge with 60 mg DL-fenfluramine, which was given orally, blood for determination of platelet MAO-B activity was drawn. Blood samples for determination of serum prolactin and serum cortisol were drawn at baseline and thereafter every hour for the following six hours. In addition, body temperature was measured at the same time-points. Δ-values were calculated as the difference between the baseline values and the highest (prolactin and cortisol) or lowest value (temperature) thereafter. There was a strong positive correlation (r = 0.75, p < 0.02) between platelet MAO-B activity and Δ-prolactin. No correlations were found to Δ-cortisol, Δ-temperature or any of the baseline values. The results support the notion that the peripheral marker platelet MAO-B activity is related to the function of the central serotonergic neurotransmitter system as assessed by the prolactin response to 60 mg DL-fenfluramin.

Changes in mental well-being during Minnesota treatment

The present study assessed mental well-being daily in 28 alcohol-dependent patients who underwent 28 days of Minnesota inpatient treatment. The Swedish Mood Adjective Check List (sMACL) with six bipolar dimensions was used for daily self-reports. At start of treatment, patients had lower levels in four dimensions of mental well-being compared to those of a norm group. Moreover, patients showed significant improvements in all levels of mental well-being during treatment, and at the end of treatment patients had values within the normal range, except for one dimension (activation/deactivation), in which the levels were significantly higher. The findings may suggest a beneficial effect of this type of treatment on mental well-being, although findings may also reflect a mere effect of adjustment to treatment or the social situation.

Mental well-being in subjects with long-term excessive alcohol consumption: an experimental study.

Daily self-reports on six dimensions of mental well-being, with the use of the Swedish Mood Adjective Check List (sMACL), were investigated in 61 socially stable and physically and mentally healthy subjects with long-term excessive alcohol consumption (113 +/- 42 g of pure alcohol daily) during a 7-week study. At the start of the study, all subjects had low levels of mental well-being compared with those for a norm group, most markedly among those who did not complete the study period (n = 20). At the end of the investigation, subjects who completed the study (n = 41) had levels of mental well-being similar to those of a norm group. Subjects who reduced their alcohol consumption by 60% did not differ in levels of mental well-being compared with subjects without reduction in intake. No differences in levels of mental well-being were observed in subjects treated with citalopram compared with those given placebo.

Inverse relationship between central serotonergic neurotransmission and blood pressure in alcohol-dependent male subjects

Summary.Data has accumulated indicating an inverse relation between central serotonergic (5-HT) neurotransmission and blood pressure in hypertensive rats and in healthy individuals. The present study aimed to elucidate whether an inverse relation exists between systolic (SBP) and diastolic (DBP) blood pressure levels and central 5-HT neurotransmission also in a group of alcohol-dependent individuals. Central 5-HT neurotransmission was assessed by using the maximum prolactin (PRL) responses to the 5-HT probe DL-fenfluramine (DL-FEN; 60 mg po) in 17 alcohol-dependent male subjects investigated during a period of on-going alcohol intake. BP was measured immediately before all time points for blood sampling, and readings before DL-FEN administration were used as the subjects resting BP. Results showed that there were inverse correlations between the maximum PRL responses to DL-FEN and the SBP levels (r = −0.57, p < 0.002) and with the DBP levels (r = −0.52, p < 0.05), respectively. The present study suggests the existence of an association between central 5-HT neurotransmission and blood pressure regulation also in alcohol-dependent individuals.