Sex hormone activity in alcohol addiction: integrating organizational and activational effects.

Abstract:

:There are well-known sex differences in the epidemiology and etiopathology of alcohol dependence. Male gender is a crucial risk factor for the onset of alcohol addiction. A directly modifying role of testosterone in alcohol addiction-related behavior is well established. Sex hormones exert both permanent (organizational) and transient (activational) effects on the human brain. The sensitive period for these effects lasts throughout life. In this article, we present a novel early sex hormone activity model of alcohol addiction. We propose that early exposure to sex hormones triggers structural (organizational) neuroadaptations. These neuroadaptations affect cellular and behavioral responses to adult sex hormones, sensitize the brain's reward system to the reinforcing properties of alcohol and modulate alcohol addictive behavior later in life. This review outlines clinical findings related to the early sex hormone activity model of alcohol addiction (handedness, the second-to-fourth-finger length ratio, and the androgen receptor and aromatase) and includes clinical and preclinical literature regarding the activational effects of sex hormones in alcohol drinking behavior. Furthermore, we discuss the role of the hypothalamic-pituitary-adrenal and -gonadal axes and the opioid system in mediating the relationship between sex hormone activity and alcohol dependence. We conclude that a combination of exposure to sex hormones in utero and during early development contributes to the risk of alcohol addiction later in life. The early sex hormone activity model of alcohol addiction may prove to be a valuable tool in the development of preventive and therapeutic strategies.

journal_name

Prog Neurobiol

journal_title

Progress in neurobiology

authors

Lenz B,Müller CP,Stoessel C,Sperling W,Biermann T,Hillemacher T,Bleich S,Kornhuber J

doi

10.1016/j.pneurobio.2011.11.001

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

136-63

issue

1

eissn

0301-0082

issn

1873-5118

pii

S0301-0082(11)00207-3

journal_volume

96

pub_type

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