- 270 Downloads
The stage in human and nonhuman animal development through which a juvenile becomes a reproductively and behaviorally mature adult.
Adolescence is a developmental stage in an animal’s life history that is characterized by both reproductive and behavioral maturation. The terms “puberty” and “adolescence” are often used interchangeably as synonyms. However, it is more accurate to consider adolescence as the period in which an animal transitions into an adult that is reproductively, socially, and cognitively mature (Sisk and Foster 2004), encompassing puberty, which more precisely is the process through which an individual becomes reproductively mature. Specialists in this area argue that reproductive (gonadal) development and behavioral development are distinct processes, driven by separate neurobiological mechanisms, that are linked by interactions between gonadal steroid hormones and the nervous system (Sisk and Foster 2004).
Adolescence is a period that is typically associated with marked changes in cognition and social behavior that include a weakened ability to regulate affect and behavior, increased reactivity to stressors, an increase in risk-taking behavior, and a greater social awareness (Crone 2009; Spear 2009; Steinberg 2005). These changes in behavior and cognition could be thought of as forming two distinct categories, primary and secondary. Primary changes contribute directly toward maturation, such as improvements in executive function, and development of sexual behavior. The reorganization of neural circuitry and increase in gonadal steroid hormones required to enact the primary changes lead to temporary secondary changes associated with psychological vulnerability such as increased sensitivity to stressors, increased risk-taking behavior, and weaker regulatory control of behavior and affect (Schulz and Sisk 2016; Steinberg 2005).
Although all vertebrate species undergo a period of transition to become reproductively and behaviorally mature (Ball and Wade 2013), mammalian species, particularly primates and rodents, are the dominant focus in scientific literature on this period of development.
The Role of Hormones in the Onset of Puberty
In primates and sheep, the hypothalamic-pituitary-gonadal (HPG) axis (comprising the hypothalamus, anterior pituitary, and gonads) is active during prenatal life and infancy, is suppressed during a prepubertal period of development, and then reactivates and matures throughout puberty resulting in reproductive maturation (Delemarre-Van De Waal 2002; Plant 2015; Plant and Zorub 1982). The HPG axis reactivates when gonadotropin-releasing hormone (GnRH) is secreted by the hypothalamus following stimulation by the neuropeptide kisspeptin (Clarke et al. 2015; Irwig et al. 2004). GnRH is released into the blood stream in pulses and stimulates the secretion of two gonadotrophins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), from the anterior pituitary gland. Gonadal development is triggered by this release of LH and FSH, which stimulates ovarian follicles to produce estrogens and progesterone, as well as stimulating the Leydig cells in the testis to produce testosterone.
In contrast to primates and sheep, which experience an extended window of prepubertal development and reactivation of the HPG, spermatogenesis in rats and hamsters begins shortly after birth at days 5 and 9, respectively (van Haaster and de Rooij 1993), and the rise in pubertal hypothalamic activity in rodents is not thought to be part of a reactivation of the HPG axis (Plant 2015).
While puberty is associated with clear physiological markers, adolescence is a period of gradual change, and there are no distinct physiological markers that indicate its beginning and end. In rats, the window within which adolescence occurs is widely considered to be days 28–42 after birth, with adulthood being reached by day 60, while some use a less conservative classification and consider adolescence to occur between days 21 (the typical onset of weaning) to 59 (McCormick and Mathews 2010). Although adolescence in humans is typically thought of as occurring during the teenage years, hormonal and organizational brain changes begin between 9 and 10 years in females and 10 and 12 years in males (Peper and Dahl 2013). The visible signs of puberty typically thought to signal its onset (such as onset of menarche in females, pubic hair growth, and sexually dimorphic physical changes) actually occur toward the final stages of puberty. If we define human adolescence as beginning and ending according to the maturation of the brain, then this period of human development could be considered to begin around the age of 10 and cease in the mid to early 20s (Sisk and Zehr 2005).
Neurological Development in Adolescence
Steroid hormones have two methods of action in the nervous system: activational or organizational. The activational effect of steroid hormones is temporary and typically associated with the adult response to its presence or absence (Sisk and Zehr 2005). Of most relevance to adolescence is the organizational effect that steroid hormones play in reorganizing the nervous system, which is a permanent change. There is a large body of evidence indicating that neurological development continues throughout adolescence. In both human and nonhuman animals, reorganization of neural circuitry occurs during adolescence, using many of the same processes involved in the original formation of the nervous system, including programmed cell death (apoptosis), neurogenesis, dendritic pruning, and sexual differentiation (Schulz and Sisk 2016). The structural changes associated with this adolescent neural reorganization are sex and brain region specific (Sisk and Zehr 2005).
In addition to reorganization and activation of the neural circuits associated with reproductive behavior, regions of the mammalian brain associated with emotional regulation, behavioral inhibition, and risk/reward judgments are especially impacted by changes in brain structure and function (Steinberg 2005). Areas of the medial and dorsal prefrontal cortex and the ventral prefrontal cortex are integral to cognitive regulation of goal-directed behavior and affective response (Nelson et al. 2005). Adolescent developmental changes in these areas involve pruning and increased myelination of synaptic networks responsible for social cognition and appear to be driven by gonadal-independent development (Nelson et al. 2005). The regions of the brain associated with affective responses to rewards and punishers include the nucleus accumbens, amygdala, and hypothalamus, and in contrast to those brain regions responsible for cognitive regulation, these regions are heavily imbued with gonadal steroid receptors which moderate considerable reorganization during puberty as a result of gonadal development (Nelson et al. 2005). However, adolescent reorganization of the regions necessary for the expression of reproductive behavior is activated both by gonadal steroid hormones and unknown gonadal steroid-independent mechanisms (Sisk and Foster 2004).
That some aspects of neurological remodeling of the adolescent brain can occur independently of gonadal maturation highlights the fact that reproductive and behavioral maturation are distinct, though entwined, processes (Sisk and Foster 2004). For example, the ability to express reproductive behavior in hamsters is reliant upon both gonadal maturation and steroid-independent adolescent maturation, as copulatory behavior can be artificially triggered by testosterone in castrated hamsters after puberty (Schulz et al. 2004), but not before (Romeo et al. 2002). Indeed, that puberty and adolescence are linked but not the same thing has considerable consequences for long-term behavioral outcomes of hormone-brain interactions when the timing of pubertal and non-pubertal changes during adolescence differ.
The timing of gonadal maturation in mammals can be impacted by a number of extrinsic factors, including calorie intake, calcium levels, extreme exercise, and even the quality of the infant-parent relationship and familial stress (Belsky et al. 2010). A mismatch in the timing of gonadal maturation and adolescent brain reorganization could have considerable effects on individual differences and risk of psychopathologies in adulthood (Sisk and Zehr 2005), and further research on the behavioral outcomes of hormone-brain interactions during puberty and adolescence is warranted (Sisk and Foster 2004). In human females, early gonadal maturation has been consistently associated with greater risks of clinical depression and eating disorders, in addition to problems with substance use (Golub et al. 2008); however, these results are confounded by problems of study design and are associations, not causation, so may be caused by correlations with unaccounted for confounding variables such as familial stress.
Differences in Cognition and Behavior During Adolescence
Adolescence triggers the emergence of considerable behavioral changes as the juvenile animal develops into the adult. Some of these changes are associated only with the adolescent phase, while others are permanent. Some of the most distinct changes are the emergence of reproductive behavior, agonistic and impulsive behavior and stress reactivity.
In rodents, the emergence of reproductive behavior occurs 1–2 weeks after pubertal testosterone increases in males and 1–2 weeks after vaginal opening in females (Sisk and Zehr 2005). To elicit reproductive behavior, the maturation of the gonadal axis alone isn’t enough. Steroid-independent and steroid-dependent organizational changes in the brain are required during adolescence to enable these behaviors to be activated by gonadal steroid hormones and to function without impairment. Indeed, if gonadal hormones are absent during adolescent neurological development, it can cause long-lasting impairments to reproductive behavior (Sisk and Zehr 2005). Examples of typical reproductive behaviors in mammals that are activated by the presence of gonadal hormones after adolescent remodeling include mounting and lordosis (presenting to indicate sexual receptivity). The influence of pubertal gonadal hormones on the reproductive behavior of an animal depends on the species, sex, and timing of exposure.
Development of other adult behavioral patterns, in addition to reproductive behavior, also relies on the organizational effect of gonadal hormones. A traditional behavioral test for measuring anxiety is the open-field test, in which lower levels of activity are interpreted as reflecting greater levels of anxiety. Adult male rats are typically less active in an open-field test than adult females, and they display less social behavior in novel environments. These differences emerge during puberty and can be prevented by castration and reinstated by replacement of testosterone during puberty. Such findings clearly demonstrate the organizational effect of gonadal hormones on these anxiety-related behaviors (Schulz et al. 2009). Comparatively, gonadal hormones expressed during puberty have also been shown to have a significant organizational impact on the development of spatial cognition via studies of people with naturally occurring disorders of the HPG axis (Sisk and Zehr 2005). Specifically, the lack of gonadal hormone expression during the normative puberty age window leads to impairments in spatial cognition in adults that cannot be repaired by administration of gonadal hormone treatments after the age of 20. Flank rubbing in Syrian hamsters and territorial scent marking in tree shrews during male-male interactions are further examples of behavior that emerges during adolescence due to gonadal hormone-dependent reorganization (Sisk and Zehr 2005).
Adolescent rats show distinct adolescent-phase differences from adults in learning and memory that stem from extensive changes to the neural circuitry that mediate these processes during adolescence (McCormick and Mathews 2010). The regions of the brain that mediate the majority of learning and memory are the medial prefrontal cortex, amygdala, and hippocampus, all of which have dense corticosteroid receptors and are influenced by glucocorticoids. An example of the differences between adolescent and adult rats is the higher thresholds for tolerating aversive motivational learning exhibited by adolescent rats when compared to adults (Pautassi et al. 2008). Differences have also been demonstrated in the responses of adolescent rats to fear conditioning that imply ongoing development of the amygdala and hippocampus (McCormick and Mathews 2010). At least part of these differences in learning and memory in adolescents can be attributed to differences in the experience of stress by adolescents, impacting performance on tasks involving a stress component.
Prepubertal rats exhibit activation in response to anxiogenic drugs in the nucleus accumbens, part of the ventral striatum, while postpubertal rats exhibited activation predominantly in the prefrontal cortex (Lyss et al. 1999). It is therefore not surprising that stress-related behavior in rats differs significantly between adolescents and adults, given the developmental processes occurring in the limbic and prefrontal areas (Spear 2009). Further discussion of differences in stress response of adolescents will be described below in reference to adolescence as a sensitive period of development.
Adolescence as a Sensitive Period of Development
As stated previously, adolescence involves considerable reorganization of the brain’s neural circuitry that can occur independently of gonadal reproductive maturation during puberty. Because the organizational effects of gonadal hormones on adult behavior are only possible during the adolescent period of development, adolescence is considered to be a sensitive period for neurological development. However, even if these changes occur at the correct times, the changes themselves are associated with additional psychological vulnerability in adolescents such as increased risk-taking behavior, weaker regulatory control of behavior and affect, and increased sensitivity to stressors (Schulz and Sisk 2016; Steinberg 2005).
Spear (2000) proposed a hypothesis that the organizational changes associated with adolescent neurological remodeling lead to increased stressor reactivity via the hypothalamic-pituitary-adrenal (HPA) axis, which in turn increases the risk of developing psychopathologies in vulnerable individuals. In order to evaluate this hypothesis, it is vital to understand the role of adolescence in normally developing children, to determine whether changes in stress physiology and emotional reactivity are indeed characteristic of the transition from childhood to adolescence (Spear 2009). A set of seminal experiments published in a special edition of Developmental Psychology in 2009 focused on stress reactivity and emotional sensitivity during the transition into adolescence provide just such evidence.
Gunnar et al. (2009) examined 82 children between the ages of 9 and 15 years, recording baseline and stressor levels of salivary cortisol as a marker of HPA activation, pubertal development status, self-reported stress, and cardiac measures of sympathetic and parasympathetic activity (Gunnar et al. 2009). The results of their study indicate clear changes in the activity of the HPA axis as children transition into adolescents, observing developmental increases in cortisol under both baseline and stressor conditions. The increase in basal cortisol observed by Gunnar and colleagues was found to be associated with puberty, as opposed to simply being age-related. Their findings were strikingly similar to those of Stroud et al. (2009), who using similar psychophysiological methods were also able to provide evidence for puberty-related hyperresponsiveness to stressors (Stroud et al. 2009). Differences in baseline cortisol levels due to maturation in adolescents highlight the importance of ascertaining pre-challenge baselines of any measures being used prior to implementing challenges in behavioral tests.
It has been suggested that, in humans, this normative developmental increase in reactivity in the HPA axis and autonomic nervous system could promote a shift toward dysregulation of the stress response in at-risk individuals, leading to the development of clinical psychopathologies such as depression (Spear 2009; Stroud et al. 2009). This hypothesis promotes the consideration of adolescence as a sensitive period in which experiences during this time can have long-term impacts on an individual’s behavior and cognition. Evidence for just such an effect can be found in studies using animal models, such as the work of Chaby and colleagues (Chaby et al. 2013) who tested the impact of chronic unpredictable stress experienced by adolescent rats on their long-term cognitive bias, decision-making, coping response, and exploratory behavior. Their results showed that unpredictable stress experienced during adolescence has lasting effects on cognition and behavior of rats, which exhibited greater sensitivity to reward loss and a negative cognitive bias lasting into adulthood. Such results support the notion that chronic unpredictable stress experienced during adolescence can induce long-term negative affective states, which is likely in turn to impact upon a suite of differences as adults in cognition and executive function inducing biases in decision-making, attention toward negative stimuli, judgment, and memory (e.g. Paul et al. 2005; Shields et al. 2016). Such negative cognitive biases could have adaptive ecological significance, if, for example, an animal inhabits an area with high-predation levels (Chaby et al. 2013); however, for humans and captive/companion animals that live outside of typical ecological niches, these stress-induced alterations could have long-term detrimental impacts on their emotional and behavioral well-being.
Adolescence is a period of dramatic neurological development that is organized by both gonadal and non-gonadal hormone pathways. This period encompasses puberty, with adolescent changes typically beginning long before physiological signs of puberty are apparent and ending long after reproductive maturity is reached. Significant remodeling of the brain’s neural circuitry during this period has both short-term and long-term impacts on behavior and cognition that characterize adolescence as a sensitive period in development. Studies involving adolescent animals should take into account possible normative differences in basal levels for all response variables and consider the potential long-term impacts of testing on individual differences. Furthermore, attention should be paid to this period of development by pet owners, as chronic stress experienced during adolescence could shape stress reactivity later in life.
- Chaby, L. E., Cavigelli, S. A., White, A., Wang, K., & Braithwaite, V. A. (2013). Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence. Frontiers in Human Neuroscience, 7, 328. https://doi.org/10.3389/fnhum.2013.00328.CrossRefPubMedPubMedCentralGoogle Scholar
- Gunnar, M. R., Wewerka, S., Frenn, K., Long, J. D., & Griggs, C. (2009). Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: Normative changes and associations with puberty. Development and Psychopathology, 21(1), 69–85. https://doi.org/10.1017/S0954579409000054.CrossRefPubMedPubMedCentralGoogle Scholar
- Irwig, M. S., Fraley, G. S., Smith, J. T., Acohido, B. V., Popa, S. M., Cunningham, M. J., … Steiner, R. A. (2004). Kisspeptin Activation of Gonadotropin Releasing Hormone Neurons and Regulation of KiSS-1 mRNA in the Male Rat. Neuroendocrinology, 80(4), 264–272. https://doi.org/10.1159/000083140.CrossRefGoogle Scholar
- McCormick, C. M., & Mathews, I. Z. (2010). Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34(5), 756–765. https://doi.org/10.1016/j.pnpbp.2009.09.019.CrossRefPubMedGoogle Scholar
- Nelson, E. E., Leibenluft, E., McClure, E. B., & Pine, D. S. (2005). The social re-orientation of adolescence: A neuroscience perspective on the process and its relation to psychopathology. Psychological Medicine, 35(2), 163–174. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15841674.CrossRefGoogle Scholar
- Pautassi, R. M., Myers, M., Spear, L. P., Molina, J. C., & Spear, N. E. (2008). Adolescent but not adult rats exhibit ethanol-mediated appetitive second-order conditioning. Alcoholism, Clinical and Experimental Research, 32(11), 2016–2027. https://doi.org/10.1111/j.1530-0277.2008.00789.x.CrossRefPubMedPubMedCentralGoogle Scholar
- Schulz, K. M., Richardson, H. N., Zehr, J. L., Osetek, A. J., Menard, T. A., & Sisk, C. L. (2004). Gonadal hormones masculinize and defeminize reproductive behaviors during puberty in the male Syrian hamster. Hormones and Behavior, 45(4), 242–249. https://doi.org/10.1016/j.yhbeh.2003.12.007.CrossRefPubMedGoogle Scholar
- Stroud, L. R., Foster, E., Papandonatos, G. D., Handwerger, K., Granger, D. A., Kivlighan, K. T., & Niaura, R. (2009). Stress response and the adolescent transition: Performance versus peer rejection stressors. Development and Psychopathology, 21(1), 47–68. https://doi.org/10.1017/S0954579409000042.CrossRefPubMedPubMedCentralGoogle Scholar