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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rationale: Attention-deficit hyperactivity disorder and related pervasive developmental disorders constitute risk factors for adult alcohol abuse and antisocial behaviours, including violent offending. Objectives: The present study assessed alcohol responsiveness and hyperemotionality in neonatally 6-OHDA-treated rats, which provides an animal model for attention-deficit hyperactivity disorder. Method: Male Wistar rats were given intracerebroventricular 6-OHDA (100 µg/5 µl) or vehicle (saline-ascorbic acid) on postnatal day 3. In adulthood, we measured motor activity, defensive behaviours and ethanol responsiveness. Results: 6-OHDA resulted in depletions of brain catecholamine levels. The experimental animals were markedly hyperactive, showed increases in active defensive behaviours (fleeing) and decreases in passive defensive responses (freezing) in response to an sudden auditory signal. In tests for reactivity to the experimenter (i.e. defensiveness to innocuous stimuli), 6-OHDA rats were hyperreactive in comparison to controls. With regard to home cage 6% ethanol and water consumption, there were no differences between experimental and control rats. However, 6-OHDA rats displayed a remarkable resistance to the motor-impairing effect of alcohol (0.5-1.0 g/kg, IP). A similar hyposensitivity to the motor-suppressive effect of diazepam (5.0 mg/kg, IP) was also found. Conclusions: The present results show that adult rats exposed to 6-OHDA as neonates are motorically restless, unusually prone to respond defensively to innocuous stimuli, and considerably less sensitive to the intoxicating effects of ethanol and diazepam. [ABSTRACT FROM AUTHOR]

Male Wistar rats with continuous access to 6% ethanol solution and water in their home cages were subjected to food restriction (FR). Reduction of body weight to 80% of normal was associated with a significant increase in ethanol drinking. It is known that the stress of FR gives rise to increased corticosterone secretion, and in line with these findings it was found that the weight of the thymus (whose size is inversely related to corticosterone levels) was reduced to 55% of normal in the present FR rats. Two subsequent experiments indicated that this adrenal activation contributed to the FR-induced enhancement of alcohol drinking. Firstly, adrenalectomized rats showed no evidence of enhanced alcohol drinking during food restriction, suggesting that adrenal corticosterone hypersecretion contributes to the enhanced ethanol consumption during FR. Secondly, treatment of FR rats with the enzyme inhibitor cyanoketone, which blocks stress-induced but not basal corticosterone secretion, at least partly prevented the FR-induced increase in ethanol drinking. These results add further evidence that sustained exposure to corticosterone facilitates ethanol consumption in the rat. [ABSTRACT FROM AUTHOR]

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms. [ABSTRACT FROM AUTHOR]

Sodium outward currents were measured in human myoballs with the whole-cell recording method. The electro-chemical gradient of the sodium ions across the cell membrane was modified over a wide range by variations of the clamped membrane potential and of the internal and external soidum concentration. Up to 50 mV positive to the sodium equilibrium potential, E, the current-voltage relation is linear. At a potential 80 mV positive to E the sodium outward current has a maximum and decreases with a further increase in electrochemical gradient. Investigating the instantaneous current change in experiments in which the membrane potential was changed while the channels were already open we could exclude the possibility that the gates of activation or inactivation are responsible for this effect. Therefore we postulate that the sodium channel has a valve-like mechanism producing a negative slope conductance at highly positive membrane potentials, a current saturation with self-inhibition by the intracellular sodium concentration, and a blockade of the channel on reduction of the extracellular sodium concentration. [ABSTRACT FROM AUTHOR]