Adolescents and androgens, receptors and rewards
Section snippets
Overview
Adolescence awakens the brain to both pleasure and risk. In human teenagers, this frequently takes the form of experimentation with drugs and sex. In the United States, the median age for first intercourse in males is 16.4 years, and 65% have had intercourse by 12th grade (Kaiser Family Foundation, 2005). Likewise, this population has the highest rates of illicit drug use in the United States. According to the 2004 National Survey on Drug Use and Health, 38% of men ages 18–25 used an illicit
Adolescence as a sensitive period for brain development
Ultimately, the brain is both a trigger and a target for androgen action during adolescence. In young boys (< 12 years) and young hamsters (< 28 days of age), circulating androgens and gonadotropins are at basal levels. As secretion of luteinizing hormone from the anterior pituitary gland rises in response to hypothalamic gonadotropin-releasing hormone, circulating testosterone concentrations increase significantly. This occurs by Tanner stage II/III (14 years) in boys, and by 28 days of age in
Androgens and neural circuits for motivated behavior
Because adolescence is a transient and dynamic phase of development, it would be difficult to evaluate the adolescent brain and behavior in isolation. Instead, to appreciate the unique character of adolescence, it is helpful to contrast it with the brain and behavior of mature adults. Thus, with the focus of this paper on male sexual behavior and reward, it is important here to introduce the neural circuits for copulation and sexual motivation in adult males, including the role of gonadal
Steroid-dependent organization of behavior during adolescence
The traditional view of hormone action on adolescent behavior is based on activational effects of steroid hormones, which refer to the ability of steroids to facilitate behavior in specific social contexts by action within target cells in the neural circuits underlying behavior. Activational effects are transient in the sense that they come and go with the presence and absence of hormone, and they are typically associated with the expression of adult behavior. In contrast, organizational
Prepubertal behavioral responses to steroids
One of the enduring puzzles of adolescent behavioral development is why activation of reproductive behavior in response to steroid exposure is attenuated in prepubertal male hamsters. If low levels of androgens before puberty limit the expression of male sexual behavior in prepubertal males, then supplementing endogenous androgens in prepubertal males should elicit mating. This turns out not to be the case (Meek et al., 1997, Romeo et al., 2001, Romeo et al., 2002b), in spite of the fact that
Pharmacologic androgens
The preceding data suggest that endogenous gonadal steroids enhance motivated behaviors during adolescence. Now, what happens if one self-administers androgens at levels up to 100× normal physiologic concentrations? This is the problem of anabolic-androgenic steroid (AAS) abuse (reviewed in Brower, 2002, Clark and Henderson, 2003). A brief digression is appropriate here: all AAS are derivatives of testosterone, all AAS have a carbon skeleton with 4 fused rings, most have 19 carbons. AAS are
Reinforcing effects of androgens
Mating and fighting are each rewarding (at least if you win the fight). Male rats will press a lever repeatedly in order to copulate with a female (Everitt and Stacey, 1987). Similarly, male mice and female hamsters will form a conditioned place preference (CPP) for locations where they have previously won fights (Martinez et al., 1995, Meisel and Joppa, 1994). If AAS can enhance rewarding social behaviors above levels normally observed in gonad-intact males, it is logical to expect that
Summary
Here we review the evidence that androgens are potent mediators of adult motivated behaviors, and further, that the timing of androgen exposure during development programs androgen-dependent motivated behavior in adulthood. Anabolic steroids are fast becoming a favored drug of abuse by adolescents in the US. While AAS may not have the addictive potency of cocaine or heroin, we are just beginning to understand the potential for androgen reinforcement and addiction. In particular, as youth sports
Acknowledgments
We thank Eleni Antzoulatos, Cortney Ballard, Lucy Chu, Kelly Peters, Jennifer Triemstra, Jane Venier, Lisa Rogers, and Pamela Montalto for their assistance with these studies. This work supported by grants from the NIH (DA12843 to RIW, MH68764 to CLS, and MH070125 to KMS).
References (129)
Trajectories of brain development: point of vulnerability or window of opportunity?
Neurosci. Biobehav. Rev.
(2003)- et al.
Rewarding properties of testosterone in intact male mice: a pilot study
Pharmacol. Biochem. Behav.
(2000) - et al.
Organizational and activational effects of sex steroids on brain and behavior: a reanalysis
Horm. Behav.
(1985) - et al.
Altered extracellular levels of DOPAC and HVA in the rat nucleus accumbens shell in response to sub-chronic nandrolone administration and a subsequent amphetamine challenge
Neuroscience Lett.
(2007) - et al.
Assessment of attentional bias and mood in users and non-users of anabolic-androgenic steroids
Drug Alcohol Depend.
(1995) - et al.
Steroid metabolism in the mammalian brain: 5alpha-reduction and aromatization
Brain Res. Bull.
(1997) - et al.
Behavioral and physiological responses to anabolic-androgenic steroids
Neurosci. Biobehav. Rev.
(2003) - et al.
Anabolic-androgenic steroids and brain reward
Pharmacol. Biochem. Behav.
(1996) - et al.
Physical provocation of pubertal anabolic androgenic steroid exposed male rats elicits aggression towards females
Horm. Behav.
(2006) - et al.
Testosterone as appetitive and discriminative stimulus in rats: sex- and dose-dependent effects
Physiol. Behav.
(1992)
Self-administration of estrogen and dihydrotestosterone in male hamsters
Horm. Behav.
Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior
Brain Res.
Castration decreases extracellular, but increases intracellular, dopamine in medial preoptic area of male rats
Brain Res.
Personality profile of men using anabolic androgenic steroids
Horm. Behav.
Psychological and serum homovanillic acid changes in men administered androgenic steroids
Psychoneuroendocrinology
Chronic anabolic-androgenic steroid treatment during adolescence increases anterior hypothalamic vasopressin and aggression in intact hamsters
Psychoneuroendocrinology
Neurogenesis decreases during brain maturation from adolescence to adulthood
Pharmacol. Biochem. Behav.
Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: effects on reproductive function
Neuropharmacology
Neurobiology of male sexual behavior
Male sexual behavior
Chronic administration with nandrolone decanoate induces alterations in the gene-transcript content of dopamine D(1)- and D(2)-receptors in the rat brain
Brain Res.
Dopaminergic effects after chronic treatment with nandrolone visualized in rat brain by positron emission tomography
Prog. Neuro-Psychopharmacol. Biol. Psychiatry
Affective properties of intra-medial preoptic area injections of testosterone in male rats
Neurosci. Lett.
Increased aggressive responding in male volunteers following the administration of gradually increasing doses of testosterone cypionate
Drug Alcohol Depend.
The effect of sub-chronic nandrolone decanoate treatment on dopaminergic and serotonergic neuronal systems in the brains of rats
Brain Res.
Neurosteroid modulation of GABAA receptors
Prog. Neurobiol.
Brain development in children and adolescents: insights from anatomical magnetic resonance imaging
Neurosci. Biobehav. Rev.
Ontogeny of the dopamine innervation in the nucleus accumbens of gerbils
Brain Res.
Successful intermale aggression and conditioned place preference in mice
Physiol. Behav.
Actions of testosterone in prepubertal and postpubertal male hamsters: dissociation of effects on reproductive behavior and brain androgen receptor immunoreactivity
Horm. Behav.s
Conditioned place preference in female hamsters following aggressive or sexual encounters
Physiol. Behav.
Anabolic-androgenic steroid exposure during adolescence and aggressive behavior in golden hamsters
Physio. Behav.
Up-regulation of androgen receptor immunoreactivity in the rat brain by androgenic-anabolic steroids
Brain Res.
Hormone dependent sex dimorphisms in the golden hamster (Mesocricetus auratus)
Physiol. Behav.
The diagnosis and reproductive outcome after surgical treatment of the complete septate uterus, duplicated cervix and vaginal septum
Am. J. Obstet. Gynecol.
Maturation of white matter in the human brain: a review of magnetic resonance studies
Brain Res. Bull.
Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms
Neuroscience
Sexual behavior enhances central dopamine transmission in the male rat
Brain Res.
The development of sex differences in the locus coeruleus of the rat
Brain Res. Bull.
Anabolic-androgenic steroid use among 133 prisoners
Comp. Psychiatry
Effects of testosterone metabolites on copulation, medial preoptic dopamine, and NOS-immunoreactivity in castrated male rats
Horm. Behav.
Effects of testosterone metabolites on copulation and medial preoptic dopamine release in castrated male rats
Horm. Behav.
Testosterone restoration of copulatory behavior correlates with medial preoptic dopamine release in castrated male rats
Horm. Behav.
Postnatal neurogenesis in the vasopressin and oxytocin-containing nucleus of the pig hypothalamus
Brain Res.
Serotonin-1A receptor activity and expression modulate adolescent anabolic/androgenic steroid-induced aggression in hamsters
Pharmacol. Biochem. Behav.
Puberty and the maturation of the male brain and sexual behavior: recasting a behavioral potential
Neurosci. Biobehav. Rev.
Dihydrotestosterone activates sexual behavior in adult male hamsters but not in juveniles
Physiol. Behav.
Estrogen receptor immunoreactivity in prepubertal and adult male Syrian hamsters
Neurosci. Lett.
Pheromones elicit equivalent levels of Fos-immunoreactivity in prepubertal and adult male Syrian hamsters
Horm. Behav.
Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters
Hormon. Behav.
Cited by (95)
Early risk factors in early-onset psychosis
2023, Adolescent Psychosis: Clinical and Scientific PerspectivesPuberty contributes to adolescent development of fronto-striatal functional connectivity supporting inhibitory control
2022, Developmental Cognitive NeuroscienceSex differences in opioid receptor mediated effects: Role of androgens
2022, Neuroscience and Biobehavioral Reviews