Adolescence is a complex developmental period characterized by sexual and brain maturation. Stress during adolescence, as abandonment and social isolation, interferes with maturation of higher brain functions such as decision making, learning and memory. Since rats are social animals, we investigate the consequences of housing rats individually during adolescence on the development of addictive behaviors. From postnatal day 23 (weaning), male and female rats were either housed in groups of the same sex or single housed throughout the experiments. At day 35 they were tested for their locomotor response to cocaine (15 mg/kg). Our results indicate that isolation during adolescence increases the locomotor response to cocaine in drug‐naive female rats. Unlike females rats, isolation during the adolescence does not affect the initial locomotor response to cocaine in males. However, these prepubertal males that normally do not show cocaine sensitization at this age, sensitized to cocaine when reared in isolation during adolescence. These results show that rearing rats in isolation exacerbates the behavioral effects of cocaine, and that the effect varies according to the sex of the animal. They also advocate for closer monitoring of neglected and solitary adolescents since they may be at a higher risk to develop drug dependency.Support or Funding InformationThis work supported by NSF under grant #OISE1545803.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Adolescence is a developmental period characterized by neuronal growth. Environmental factors such as maternal neglect, social stress and drugs of abuse have a direct impact on future behavioral patterns. Because rats are highly social animals, we decided to investigate if isolation stress during adolescence increases conditioned place preference (CPP) to drugs of abuse. Since lower D2 receptor expression in the mesocorticolimbic system is known to increase cocaine conditioning in adult animals, and because adolescents and adults differ in dopaminergic connectivity and D2 receptor populations, we investigated if D2 receptors are altered during these conditions. Female rats were weaned at postnatal day 23 and housed singly or in pairs. At day 34 rats were tested in an open field, at day 35 in an elevated plus maze and at day 36 they were tested for CPP to cocaine (15mg/kg). At post‐natal day 48, rats were euthanized, brains collected and stored at −80°C. Single‐housed rats showed greater conditioning to cocaine when compared to group‐housed rats. This suggest that housing rats singly increases the rewarding properties of cocaine. Single‐housed rats also show lower D2 receptor immunoreactivity in the Nucleus accumbens (NAc) and the Prefrontal cortex (PFC) when compared to group‐housed rats. This correlates with the greater conditioning observed in single housed rats. Isolation stress had the effect of lowering D2 receptor populations in the NAc and PFC thus augmenting the rewarding properties of cocaine in adolescent female rats. Chronic stress during adolescence thus can lower D2 receptors and could be a determining factor in substance abuse and relapse. Support or Funding Information Financial assistance was provided by the Office of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE‐#1545803).

Anabolic androgenic steroids (AAS) are known to affect mood and motivational behaviors. One of the AAS most commonly used by young adults is nandrolone. In 2017, prevalence of cocaine use in this population was approximately 33% compared to 4.9% in the rest of this population. Cocaine and AAS increase risk taking behaviors. However, the link between the use of AAS during adolescence and propensity to use other drugs of abuse has not been clearly established. In this study, adolescent female rats were administered nandrolone decanoate (20mg/kg/sc) or vehicle for 10 successive days starting on day 28, the rats were then divided into 4 groups; Oil‐Saline, ND‐Saline, Oil‐cocaine and ND‐cocaine. Beginning on day 40, they were tested for locomotor sensitization to cocaine. From days 1–5 and at days 13 and 23 rats received an injection of cocaine (15 mg/kg/ip). Their locomotor response to cocaine was measured at days 1, 5, 13 and 23. Our data show that nandrolone enhances cocaine sensitization in female rats. In ovarian tissue, it reduced weight and induced cysts formation. These data show that exposure to supra‐physiological levels of androgens during adolescence modifies the brain circuitry that regulates addictive behaviors increasing the psychoactive properties of cocaine. AAS also have detrimental effects on the female reproductive system and on fertility.Support or Funding InformationFinancial assistance was provided by the Office of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) program (OISE #1545803).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly used AAS by young adults is nandrolone. Use of AAS has been associated with increased risk of steroid dependence, mood disorders and polysubstance use. Indeed, cocaine use among AAS users is approximately 33% compared to 4.9% in the rest of the population. The effect of nandrolone (ND) use during adolescence on female motivational behaviors and on the reproductive system has not been investigated. Adolescent female rats were divided into two groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. On day 38 rats were tested on an Open Field and on day 39 in an Elevated Plus Maze. On day 40, the rats were then divided into 2 additional groups for a total of 4 groups: Oil‐Saline, ND‐Saline, Oil‐Cocaine and ND‐Cocaine and tested for locomotor sensitization to cocaine. From days 40‐44 and at days 52 and 62 rats received an injection of cocaine (15 mg/kg/ip) or saline. Their locomotor response to cocaine was measured at days 40, 44, 52 and 62. Our data show that nandrolone treated rats spent more time in the center of the open field, have no preference between open and closed arms of the plus maze and show augmented locomotor response to cocaine on days 5 and 13 compared to oil treated rats. This suggests that nandrolone increases risk taking behavior and the psychoactive properties of cocaine while having no effect on anxiety. In addition, nandrolone reduced ovarian weight and increased the formation of ovarian cysts. In contrast, in the uterus, it increased uterine weight and hindered endometrial growth. These data show that exposure to supra‐physiological levels of androgens during adolescence induces neurochemical changes in brain circuitry that regulate emotions and increases the psychoactive properties of cocaine. Nandrolone also severely impairs reproductive function, inducing formation of ovarian cysts and altering uterine morphology, an effect that is exacerbated when paired with cocaine.