Date of Award

1-1-2011

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Psychology

Program

Behavioral Neuroscience

Content Description

1 online resource (vii, 212 pages) : illustrations.

Dissertation/Thesis Chair

Cheryl A Frye

Committee Members

Joseph F DeBold, Mitch Earleywine, Ronald S Friedman, Augustus R Lumia

Keywords

5alpha-reductase, Aggression, Androgen Receptor, Social Dominance, Social Interaction, Testosterone, Aggressive behavior in animals, Inter-male aggression, Alcohol, Social behavior in animals, Mice as laboratory animals

Subject Categories

Neuroscience and Neurobiology | Pharmacology | Psychology

Abstract

Androgenic steroids, such as testosterone, may influence the propensity for aggression in both people and animals. Some of testosterone's effects on aggression may be due, in part, to its metabolic products that are 5á-reduced and 3á-hydroxylated to form, 3á-androstanediol (3á-diol), which can also enhance aggression in mice. Notably, alcohol (EtOH) consumption facilitates aggression in people and animals, particularly among those predisposed to act aggressively. In rats, EtOH can increase 3á-diol in prefrontal cortex, which may facilitate aggression. The present work aimed to elucidate the role of 3á-diol for EtOH-enhanced aggression. We hypothesized that EtOH would enhance inter-male aggression, social dominance, and 3á-diol formation in frontal cortex of mice. Specifically, we propose that some of the effects of gonadal steroids would independent of actions at androgen receptors (the cognate intracellular target of testosterone) and would require actions of 5á-reductase (an enzyme that is necessary for formation of 3á-diol). To assess this, behavioral analyses for inter-male aggression and/or social dominance were conducted on gonadally-intact, or GDX, mice that were wildtype (B6:129S7), testicular feminized mutants (TFMs; which have natural androgen receptor insensitivity) on a B6 background, or 5á-reductase type 1 knockouts (5á-RKO; which lack the type I isoform of 5á-reductase) on a B6:129S7 background. Mice were administered EtOH (1.0 g/kg, IP) 15 mins prior to testing. Concentrations of 3á-diol in frontal cortex and serum were assessed via radioimmunoassay; protein expression of androgen receptor and 5á-reductase type 1 were also assessed via western blot analyses. EtOH significantly increased inter-male aggression, concomitant with increased 3á-diol in frontal cortex, among gonadally-intact and GDX wildtype, but not 5á-RKO, mice. TFM mice did not readily demonstrate spontaneous inter-male aggression. Assessment of social dominance revealed that EtOH significantly increased the number of trials won, and the number of aggressive acts displayed, among wildtype and TFM mice that were dominant or had not previously established dominance. EtOH did not enhance pushing behavior in the social dominance task among 5á-RKO mice, or subordinate mice of any strain. EtOH enhanced 3á-diol in frontal cortex of wildtype or TFM mice that were non-subordinate (and to the greatest extent among those that had not previously established dominance). Serum levels of 3á-diol were not altered by EtOH in any group. The hypotheses that EtOH would enhance aggression and cortical 3á-diol, independent of androgen receptor actions, and dependent on type I 5á-reductase, were upheld. These data suggest that the neurosteroid metabolite, 3á-diol, may play an important role in EtOH-enhanced aggression, perhaps via disinhibitory actions in the frontal cortex.

Download

Share

COinS