Elsevier

Hormones and Behavior

Volume 53, Issue 2, February 2008, Pages 378-385
Hormones and Behavior

Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters

https://doi.org/10.1016/j.yhbeh.2007.11.004Get rights and content

Abstract

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual libido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27–41 days of age) or in adulthood (63–77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior.

Introduction

Adolescence is the developmental transition from childhood to adulthood and it encompasses reproductive, neural, and behavioral maturation (Andersen, 2003, Casey et al., 2000, Lenroot et al., 2007, Sisk and Foster, 2004, Sisk and Zehr, 2005, Spear, 2000, Yurgelun-Todd, 2007). The onset of puberty marks the onset of adolescence, and gonadal steroid hormones, which become elevated during puberty, influence subsequent adolescent brain development by both organizing and activating neural circuits underlying social behaviors (Delville et al., 1998, Primus and Kellogg, 1989, Primus and Kellogg, 1990, Romeo, 2005, Schulz and Sisk, 2006, Sisk and Foster, 2004, Spear, 2004). Importantly, the organizational effects of pubertal hormones program their activational effects in adulthood. For example, studies in the Syrian hamster show that the presence of testicular hormones during adolescence results in adults that more readily display male-typical social behaviors relative to adults that matured in the absence of testosterone (T) (Schulz et al., 2006, Schulz et al., 2004, Sisk et al., 2003). Thus, the adolescent brain is exquisitely sensitive to endogenous testicular steroids, and the action of testicular hormones during adolescence has both short-term and long-term consequences on social behaviors.

Given the significance of endogenous T in normal development of the adolescent male brain, it is important to consider how anabolic androgenic steroids (AAS) influence the adolescent brain and behavior. AAS are synthetic compounds structurally related to T that promote muscle growth (anabolic) and have masculinizing (androgenic) effects. AAS are clinically used to treat malnutrition and mood disorders (Kopera, 1993, Perry et al., 2002); however, the benefits they have for treating physiological and psychological disorders may become detriments when they are used inappropriately (Blue and Lombardo, 1999, Corcoran and Longo, 1992). Adolescents that use AAS are often described by their peers, teachers, and psychologists as defiant, aggressive, and antisocial. In addition, teenagers may display either increased or decreased sexual libido after AAS misuse (Thiblin and Petersson, 2005). In the United States, the onset of AAS use can be as early as 10 years of age, and use among high school males has been as high as 12% in the last decade (Ahima and Harlan, 1992, Bahrke and Yesalis, 2004, Bahrke et al., 1990, Bahrke et al., 1998, Buckley et al., 1988, Terney and McLain, 1990). Although there is evidence that severe consequences occur after misuse of AAS by adolescents, there has been relatively little systematic investigation of how these exogenous compounds affect the adolescent brain and behavior.

AAS affect the expression of social behaviors in most rodent models. The behavioral responses to AAS depend on the chemical structure of the steroid administered, whether steroid treatment consists of a single compound or as a cocktail, and the age and duration of treatment. Intact adult male rats treated with T and testosterone cypionate (TC) do not display altered reproductive behaviors when compared to controls (Clark et al., 1997, Farrell and McGinnis, 2003). However, T administered to intact adolescent male rats increased sexual behaviors in adulthood (Wesson and McGinnis, 2006). Also, long-term (12 weeks) treatment of intact male rats with oxymethelone, stanozolol, nandrolone, or 17α-methyltestosterone during adolescence and continuing to adulthood results in a decrease in sexual behaviors (Clark et al., 1997, Farrell and McGinnis, 2003, Feinberg et al., 1997). AAS also affect aggressive behaviors in rodents. Single compounds such as T and testosterone propionate (TP) increase aggression in intact adult male rats and mice (Albert et al., 1989, Clark and Barber, 1994, Farrell and McGinnis, 2003, Lumia et al., 1994, Martinez-Sanchis et al., 1998). However, adolescent exposure to single compounds such as nandrolone, 17α-methyltestosterone, or stanozolol has little or no effect on aggression in rats or hamsters (Breuer et al., 2001, Farrell and McGinnis, 2003, McGinnis, 2004, Wesson and McGinnis, 2006). Adolescent male Syrian hamsters exposed to a cocktail of AAS for 2 or 4 weeks show an increase in aggressive behaviors (DeLeon et al., 2002, Grimes and Melloni, 2002, Grimes et al., 2003, Melloni and Ferris, 1996, Ricci et al., 2004, Salas-Ramirez and Sisk, 2005). It is clear that a number of variables determine the overall effects of AAS on sexual and aggressive behaviors, and age has not been systematically studied.

The use of anabolic steroids by adolescent males and the growing evidence that the adolescent brain is particularly sensitive to hormones and experience call for a better understanding of how age at the time of exposure to AAS influence behavioral responses to AAS. The objective of this study was to directly compare the immediate effects of AAS on sexual and aggressive behaviors in adolescent and adult intact male Syrian hamsters. Because adolescent male hamsters are more responsive than adults to the organizational effects of endogenous testicular hormones on male social behaviors (Schulz and Sisk, 2006), we hypothesized that adolescents would also be more responsive to activational effects of exogenous AAS, leading to the prediction that AAS will elicit greater behavioral responses in adolescent compared to adult males.

Section snippets

Animals

Eighteen-day-old male Syrian hamsters (Mesocricetus auratus) were obtained from Harlan Sprague–Dawley Laboratories (Madison, WI). Upon arrival, males were housed in groups of eight animals per cage (polycarbonate, 33 × 38 × 17 cm) with ad libitum access to food (Telkad Rodent Diet No. 8640, Harlan) and water. Animal colony temperature was maintained at 22 ± 2 °C, and animals were kept on a light–dark cycle of 14:10 L:D (lights off at 1600 h EST). At 25 days of age, animals were singly housed in

Experiment 1: the effects of AAS on sexual behaviors in adolescent and adult male Syrian hamsters

AAS did not affect the amount of time that either adolescents or adults spent investigating the receptive female (data not shown). There was a significant interaction between treatment and age on the number of mounts [F(1, 27) = 17.172; p < 0.0002], intromissions [F(1, 27) = 7.449; p < 0.01], and ejaculations [F(1, 27) = 15.005; p < 0.0006]. In general, AAS facilitated reproductive behavior in adolescent hamsters and reduced reproductive behavior in adults (Fig. 1). Post hoc analyses showed a trend toward

Discussion

These experiments demonstrate that 2-week treatment of male hamsters with a cocktail of testosterone cypionate, boldenone undecylenate, and nandrolone decanoate at doses comparable to what a heavy or chronic AAS user would administer leads to increased levels of aggressive and reproductive behaviors in adolescent males as compared to both vehicle-treated adolescents and AAS-treated adults. This is the first direct comparison of the behavioral effects of anabolic steroid exposure at two

Acknowledgments

We would like to thank Lisa Rogers, Sara Hunter, Jane Venier, and Anibal Rivera-Rivera for their technical support. We would also like to thank Kalynn Schulz, Eman Ahmed, Heather Molenda-Figueira, Margaret Bell, and Julia Zehr for their feedback during the editing of this manuscript. Lastly, we would like to thank the ULAR staff Constance Montville Crew, Bernadette Bentley, and Patrick Lee for always providing our animals with excellent care. This work was funded by NIH R01-MH068764 awarded to

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