Effects of chronic exposure to an anabolic androgenic steroid cocktail on alpha5-receptor-mediated GABAergic transmission and neural signaling in the forebrain of female mice.

Full Abstract

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone that are illicitly self-administered for enhancement of performance and body image, but which also have significant effects on the brain and on behavior. While the stereotypical AAS user is an adult male, AAS abuse in women is rapidly increasing, yet few studies have examined AAS effects in female subjects. We have assessed the effects in female mice of a combination of commonly abused AAS on neuronal activity and neurotransmission mediated by GABA type A (GABA(A)) receptors in the medial preoptic nucleus (MPN); a nexus in the circuits of the hypothalamus and forebrain that are critical for the expression of social behaviors known to be altered in AAS abuse. Our data indicate that chronic exposure to AAS resulted in androgen receptor (AR)-dependent upregulation of alpha(5), beta(3) and delta subunit mRNAs. Acute application of the alpha(5) subunit-selective inverse agonist, L-655,708 (L6), indicated that a significant fraction of the synaptic current is carried by alpha(5)-containing receptors and that AAS treatment may enhance expression of alpha(5)-containing receptors contributing to synaptic, but not tonic, currents in the MPN. AAS treatment also resulted in a significant decrease in action potential frequency in MPN neurons that was also correlated with an increased sensitivity to L-655,708. Our data demonstrate that chronic exposure to multiple AAS elicits significant changes in GABAergic transmission and neuronal activity that are likely to reflect changes in the expression of alpha(5)-containing synaptic receptors within the MPN.

Author information

Author/s: Penatti, C A A (CA); Costine, B A (BA); Porter, D M (DM); Henderson, L P (LP);

Affiliation: Department of Physiology, Dartmouth Medical School, Hanover, NH 03755, USA.

Grants: DA14137 (Agency:NIDA NIH HHS) ; DA18255 (Agency:NIDA NIH HHS) ; DK07508 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2009-Jun; vol 161 (issue 2) : pp 526-37

Dates: Created 2009/06/01; Completed 2009/08/19;

PMID: 19324077, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Action Potentials
Anabolic Agents - administration & dosage; adverse effects
Androgens - administration & dosage; adverse effects
Animals
Drug Interactions
Female
Imidazoles - pharmacology
Methyltestosterone - administration & dosage; adverse effects
Mice
Mice, Inbred C57BL

Nandrolone - administration & dosage; adverse effects; analogs & derivatives
Neurons - drug effects; physiology
Preoptic Area - cytology; drug effects; physiology
Protein Subunits - agonists; physiology
RNA, Messenger - biosynthesis
Receptors, Androgen - physiology
Receptors, GABA-A - agonists; biosynthesis; physiology
Signal Transduction - drug effects
Synaptic Transmission
Testosterone - administration & dosage; adverse effects; analogs & derivatives

Associated Chemicals: Anabolic Agents (0) ; Androgens (0) ; Imidazoles (0) ; L 655,708 (0) ; Protein Subunits (0) ; RNA, Messenger (0) ; Receptors, Androgen (0) ; Receptors, GABA-A (0) ; nandrolone decanoate (360-70-3) ; Nandrolone (434-22-0) ; Methyltestosterone (58-18-4) ; testosterone 17 beta-cypionate (58-20-8) ; Testosterone (58-22-0)

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