Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational stress than to intrinsic factors. In further studies, it should be investigated, whether the present results also apply to stress and human alcohol drinking.

Benzyl alcohol increases voluntary ethanol drinking in rats.

The anabolic steroid nandrolone decanoate has been reported to increase voluntary ethanol intake in Wistar rats. In recent experiments we received opposite results, with decreased voluntary ethanol intake in both high drinking AA and low drinking Wistar rats after nandrolone treatment. The difference between the two studies was that we used pure nandrolone decanoate in oil, whereas in the previous study the nandrolone product Deca-Durabolin containing benzyl alcohol (BA) was used. The aims of the present study were to clarify whether the BA treatment could promote ethanol drinking and to assess the role of the hypothalamic-pituitary-adrenal-gonadal axes (HPAGA) in the potential BA effect. Male AA and Wistar rats received subcutaneously BA or vehicle oil for 14 days. Hereafter followed a 1-week washout and consecutively a 3-week voluntary alcohol consumption period. The median (± median absolute deviation) voluntary ethanol consumption during the drinking period was higher in BA-treated than in control rats (4.94 ± 1.31 g/kg/day vs. 4.17 ± 0.31 g/kg/day, p = 0.07 and 1.01 ± 0.26 g/kg/day vs. 0.38 ± 0.27 g/kg/day, p = 0.05, for AA and Wistar rats, respectively; combined effect p < 0.01). The present results can explain the previous discrepancy between the two nandrolone studies. No significant BA effects on basal and ethanol-mediated serum testosterone and corticosterone levels were observed in blood samples taken at days 1, 8 and 22. However, 2h after ethanol administration significantly (p = 0.02) higher frequency of testosterone elevations was detected in high drinking AA rats compared to low drinking Wistars, which supports our previous hypotheses of a role of testosterone elevation in promoting ethanol drinking. Skin irritation and dermatitis were shown exclusively in the BA-treated animals. Altogether, the present results indicate that earlier findings obtained with Deca-Durabolin containing BA need to be re-evaluated.

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction.

Profile of a drunk driver and risk factors for drunk driving. Findings in roadside testing in the province of Uusimaa in Finland 1990-2008.

The aim of the present study was to define the profile of a drunk driver and to determine risk factors for drunk driving by analyzing data on both sober and drunk drivers. Systematic roadside surveys have been carried out in Southern Finland for over 18 years, with 20,000-30,000 drivers breath tested annually. During the study period, 1241 drunk drivers were caught (legal blood alcohol limit 0.50‰). The comparison material consisted of 3407 sober drivers. The surveys were designed to further investigate demographic features and driving habits of drivers. The prevalence of drunk driving has been 0.2% over the time period, with only random variations. According to the data, a typical drunk driver is a man aged 40-49 who has a valid driving license and drives his own car, usually alone, with a blood alcohol concentration (BAC) of 1.0‰. He has a job and is married or cohabiting. The profile remained consistent throughout the study period. The risk of drunk driving was found to be five times higher for men than for women. Divorcees and widow(er)s had a substantially higher risk factor for being caught drunk driving than married drivers. Drunk drivers are most likely to be caught by roadside testing on Saturday mornings. During the study period the blood alcohol limit for aggravated drunk driving was lowered in 1994 from 1.5 to 1.2‰. In 2004 the taxation of alcohol beverages was reduced by 30%. Neither of these measures affected the prevalence of drunk driving or the mean BAC of drunk drivers (p=0.63).

Chernobyl exposure as stressor during pregnancy and hormone levels in adolescent offspring.

BACKGROUND: Animal research suggests a programming effect of prenatal stress in the fetal period, resulting in disruptions in behavioural and neuromotor development. Physiological changes that mediate these effects include alterations in the hypothalamic-pituitary-adrenal axis and in testosterone levels. This human study focuses on changes related to these physiological systems after prenatal stress exposure. METHODS: We examined the potential effect of prenatal stress associated with the Chernobyl disaster in an ongoing genetic epidemiological study in Finland. One birth cohort of twins (n = 121 twin pairs) was exposed in utero to maternal stress, and their saliva cortisol and testosterone levels at age 14 were compared with twins (n = 157 twin pairs) born one year later. RESULTS: Cortisol levels in both sexes and testosterone levels among females were significantly elevated after prenatal exposure to maternal stress from the second trimester onwards, compared to reference groups of non-exposed adolescents. Exposure explains 3% of variance (p<0.05) in cortisol levels and 18% of variance in testosterone levels (p<0.001). No significant differences were found for exposure from either first or third trimester onwards. CONCLUSION: Our results suggest that prenatal exposure to maternal stress in the second trimester of pregnancy may have resulted in prenatal programming of physiological systems relating to cortisol and testosterone levels.