Psychopharmacology (2004) 172:352–355 DOI 10.1007/s00213-003-1662-0 ORIGINAL INVESTIGATION J. M. Torres · E. Ortega Alcohol intoxication increases allopregnanolone levels in male adolescent humans Received: 7 July 2003 / Accepted: 2 September 2003 / Published online: 28 November 2003  Springer-Verlag 2003 Abstract Rationale: Teenage drinking is a cause of growing concern in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. Increased anxiety, irritability and depression among adolescents may induce them to seek the anxiolytic and rewarding properties of alcohol. Allopregnanolone is rewarding in rodents, and therefore may contribute to the effects of alcohol. Objective: In this paper, we studied the effects of acute alcohol intoxication on the plasma levels of allopregnanolone in male adolescents. Methods: Blood samples were drawn from male adolescents who arrived at the Emergency Department of the Hospital. Two groups were studied: one study group was formed by adolescents who arrived with evident behavioral symp- toms of acute alcohol intoxication (AAI) and the other by those arriving for mild trauma (contusions, sprains) after no consumption of alcohol (Controls). Results: Our results demonstrate that AAI significantly increases serum allopregnanolone levels in male adolescents. Conclu- sions: Because alcohol and allopregnanolone positively modulate gamma-aminobutyric acid type A (GABA A ) receptors, allopregnanolone may play a major role in the anxiolytic and rewarding effects of alcohol, either directly or by influencing the sensitivity of GABA A receptors to alcohol. Keywords Allopregnanolone · Progesterone · Alcohol intoxication · Adolescents · Male · Human Introduction The abuse of alcohol by young people is a widespread and growing phenomenon in developed countries (Bailey and Vallery 1993), where around one-third of habitual drinkers are under 16 years old (Shope et al. 1994). An increasing proportion of young adolescents consume alcoholic drinks every weekend. Gamma-aminobutyric acid type A (GABA A ) receptors are positively modulated by alcohol, producing sedative and anxiolytic effects. Interaction between alcohol and neurosteroids at GABA A receptors has been reported (Grobin et al. 1998). One of the most potent endogenous positive modulators of GABA A receptors is the neuro- steroid allopregnanolone, which has sedative, hypnotic, anticonvulsant and anxiolytic effects (Lambert et al. 1995). According to some animal experiments, allopreg- nanolone produced in response to systemic ethanol administration may contribute to several of the effects of ethanol that are associated with the modulation of GABA A receptors (Morrow et al. 2001a; Khisti et al. 2002). Allopregnanolone, which is rewarding in rodents (Finn et al. 1997), may contribute to the anxiolytic and rewarding effects of alcohol. We previously reported that alcohol ingestion in- creased circulating allopregnanolone levels in female adolescent humans (Torres and Ortega 2003). Ovary and adrenal cortex may be the major sources of circulating allopregnanolone in fertile women (Genazzani et al 1998, 2002). The contribution of ovary and adrenal cortex to the increased serum levels of allopregnanolone in female adolescents in response to alcohol is therefore not clear. If the ovary contributes significantly to the increased serum allopregnanolone levels in women after alcohol ingestion, the effects of alcohol on circulating allopregnanolone may be different between males and females. The present study aimed to determine allopreg- nanolone levels in situations of acute alcohol intoxication (AAI) in male adolescent humans, in which the adrenal cortex is the only source of circulating allopregnanolone. J. M. Torres · E. Ortega ( ) ) Department of Biochemistry and Molecular Biology, Institute of Neurosciences, Faculty of Medicine, University of Granada, Avda. de Madrid s/n, 18012 Granada, Spain e-mail: esortega@ugr.es Tel.: +34-958-243519 Fax: +34-958-249015