Although anabolic-androgenic steroids (AAS) have legitimate medical uses, they are also drugs of abuse. AAS are taken in large quantities by athletes and others to increase performance, with negative long-term health consequences. In 1991, testosterone was declared a controlled substance. Nonetheless, illicit use of AAS continues to increase, particularly among adolescents. Indeed, the incidence of steroid use among high school seniors is comparable to that for cocaine or heroin. Although users defend performance enhancing substances as a """"""""healthy lifestyle choice"""""""", clinical studies and anecdotal reports present a different picture. Inappropriate and excessive agonistic behavior ('roid rage) is the most widely-reported psychiatric side effect of AAS in humans. Heightened sexuality and sexual violence have also been noted. Furthermore, AAS are linked with polydrug abuse, most notably opioids. We hope to understand why AAS abuse predisposes individuals to engage in inappropriate and excessive aggression, sexual behavior and drug use, and to unravel the underlying neural mechanisms. In particular, we aim to address a major public misconception that 'roid rage represents a loss of control, a sudden and exaggerated response to a minimal provocation. Instead, research suggests that AAS-treated rats remain sensitive to the context (individual and environment) of social interactions. This suggests a new explanation for behavioral effects of AAS abuse. The current proposal focuses on our hypothesis that chronic exposure to AAS during adolescence inappropriately increases responsiveness to rewarding stimuli, both natural rewards (sex, aggression) and drugs of abuse. The proposed studies will investigate how high-dose androgens in adolescent rats alter reward processes. Understanding behavioral effects of AAS use in humans is complicated by the user's motivation for increased strength and muscle mass. Animal studies can evaluate responses to AAS in an experimental context where appearance and athletic performance are irrelevant. In this regard, animals also demonstrate AAS-induced aggression and sexual behavior. Yet, these studies have emphasized consummatory aspects of behavior, not the appetitive motivation for mating or fighting. Importantly, sex, fighting and drug use are each reinforcing, and each is sensitive to androgens. Accordingly, we hypothesize that AAS increase expression of social behaviors and drug self-administration by increasing the reward value of these steroid-sensitive behaviors.
Aim 1 will determine if AAS increase motivation for aggression (Aim 1A), mating (Aim 1B) and morphine self- administration (Aim 1C).
Aim 2 will explore neural mechanisms for these effects. We will determine if testosterone is a permissive signal to enhance dopamine activity in the nucleus accumbens in response to sexual stimuli (Aim 2A).
Aim 2 B will determine fundamental mechanisms underlying these responses by measuring levels of tyrosine hydroxylase, dopamine D1 and D2 receptors, and the dopamine transporter. Together, these studies will provide insight into the potential for AAS to enhance motivation and reward, and the mechanisms through which this occurs.
Illicit use of anabolic-androgenic steroids (AAS) is associated with aggression ('roid rage), sexual violence and polydrug abuse. We will treat adolescent male rats with testosterone to determine if AAS increase motivation for rewarding social behaviors and drug self-administration. According to our hypothesis, testosterone facilitates motivation and reward by enhancing dopamine activity in the nucleus accumbens, through a combination of increased dopamine release, reduced dopamine reuptake, and increased dopamine receptors.
| Tobiansky, Daniel J; Wallin-Miller, Kathryn G; Floresco, Stan B et al. (2018) Androgen Regulation of the Mesocorticolimbic System and Executive Function. Front Endocrinol (Lausanne) 9:279 |
| Wallin-Miller, Kathryn G; Kreutz, Frida; Li, Grace et al. (2018) Anabolic-androgenic steroids (AAS) increase sensitivity to uncertainty by inhibition of dopamine D1 and D2 receptors. Psychopharmacology (Berl) 235:959-969 |
| Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana et al. (2018) Anabolic-androgenic steroids alter decision making in a balanced rodent model of the Iowa gambling task. Behav Neurosci 132:152-160 |
| Li, Grace; Wood, Ruth I (2017) Male rats play a repeated donation game. Physiol Behav 174:95-103 |
| Donhoffner, Mary E; Al Saleh, Samar; Schink, Olivia et al. (2017) Prosocial effects of prolactin in male rats: Social recognition, social approach and social learning. Horm Behav 96:122-129 |
| Wallin-Miller, Kathryn G; Chesley, Jordyn; Castrillon, Juliana et al. (2017) Sex differences and hormonal modulation of ethanol-enhanced risk taking in rats. Drug Alcohol Depend 174:137-144 |
| Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana et al. (2016) Anabolic-androgenic steroids decrease dendritic spine density in the nucleus accumbens of male rats. Neuroscience 330:72-8 |
| Wood, Ruth I; Kim, Jessica Y; Li, Grace R (2016) Cooperation in rats playing the iterated Prisoner's Dilemma game. Anim Behav 114:27-35 |
| Wallin, Kathryn G; Alves, Jasmin M; Wood, Ruth I (2015) Anabolic-androgenic steroids and decision making: Probability and effort discounting in male rats. Psychoneuroendocrinology 57:84-92 |
| Wallin, Kathryn G; Wood, Ruth I (2015) Anabolic-androgenic steroids impair set-shifting and reversal learning in male rats. Eur Neuropsychopharmacol 25:583-90 |
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