The overall goals of this project are to assess the behavioral effects of anabolic androgenic steroids (AAS) and to understand the underlying mechanisms for these changes. An intact male rat model will be employed in order to provide empirical data on the behavioral and neuroanatomical consequences of AAS abuse. Three different classes of AAS are typically abused: testosterone esters, 19-nortestosterone esters, and 17-alpha-alkylated androgens. AAS users typically 'stack' these drugs (i.e., use several together). However, since little is known in rats about the behavioral effects of AAS other than testosterone, we propose to test the of one AAS from each category individually. The testosterone ester will be testosterone propionate (TP), the 19-nortetsosterone ester will be nandrolone (ND) and the 17-alpha-alkylated androgen will be stanozolol (ST). All are commonly abused AAS. The first two aims will investigate two frequently reported behavioral disturbances in human users: aggression and circadian rhythms.
The first aim will determine the role of contextual cues in stimulating aggression during exposure to TP, ND or ST and whether these same cues are effective during withdrawal from AAS.
The second aim will test the effects of AAS on circadian rhythms by measuring wheel running activity in 12:12 LD, phase reversal and constant dark during AAS exposure and during AAS withdrawal. Because AAS abuse is on the rise in adolescent males, the experiments proposed in the third aim will assess the effects of AAS on circadian rhythms, aggression, and reproductive function in peripubertal male rats. We will also examine whether the behavioral effects of AAS exposure during this critical period of development are reversible or permanent. To assess whether the ability of these AAS to bind to androgen receptors is related to their behavioral effects, the fourth aim will assess the binding characteristics of TP, ND and ST on androgen receptors in brain. The fifth aim will follow up our novel finding that chronic AAS exposure results in a loss of detectable cells in specific brain nuclei. We will determine if the loss of detect ability in cells of TP-treated males occurs in neurons or glia, and if the affected cells contain androgen receptors. Double label immunofluorescence and confocal microscopy will be used in conjunction with volume/size analyses to investigate the cellular characteristics of affected cells. These studies will aid in understanding the effects of AAS abuse on behavior in bot adults and juveniles, and will delineate possible mechanisms underlying AAS effects on brain.
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