Early life experiences have a lasting impact on physiology and behavior. In mammals, adolescence is a critical developmental period when various neural structures undergo extensive remodeling, and experiences during this time can have a lasting impact on growth and behavior (Sachser et al., 2010). The initiation of adolescence occurs around the same time as the onset of reproductive puberty, and the hormonal events that are hallmarks of these developmental periods target the brain creating an intricate link among these processes (Sisk & Zehr, 2005). Reproductive maturity is reached when steroid hormones present during adolescence adjust and stimulate neural circuits, leading to increases in sensitivity to sexual sensory stimuli, sexual drive, and manifestation of copulatory behaviors in particular social situations (Sisk & Foster 2004). Although there is overlap in timing of these two processes, the influence of hormones on reproductive behavior depends to some extent on changes in the adolescent brain that occur separately from gonadal maturation (Sisk & Foster 2004). Adolescence can be seen as a gradual phase of transition rather than a moment of attainment, whereas puberty is merely one of the temporally restricted adolescent points of transition (Spear, 2000). It is essential to move away from the notion that puberty is a gonadal event and recognize the start of puberty as a brain event with persistent exchanges between steroid hormones and the adolescent nervous system (Sisk& Zehr, 2005).
The hormonal changes associated with puberty and the timing of environmental events may increase vulnerability to the negative symptoms of depression (Leen-Feldner, Reardon, Hayward, & Smith, 2008). In humans, sexual experience in adolescence can increase susceptibility to mental disorders (Sabia, 2006), modify immune function (Danese et al., 2006) and alter stress reactivity (Danese et al., 2009). Hormones modify the functioning of numerous widespread neurotransmitter systems involved in emotional and cognitive brain functions (Cameron, 2004). The best known adolescence-driven brain modulations occur in prefrontal regions of the brain, stress sensitive dopamine neural circuitry, and the limbic system, which includes the amygdala, hippocampus, hypothalamus, nucleus accumbens, and areas of connection between limbic and prefrontal areas (Crews & Hodge, 2007).
Alterations in neurocircuitry that occur during the critical period of adolescence provide important information that aids in delineating processes that underlie the etiology of depressive disorders. Human studies have revealed that a positive relationship exists between early sexual activity and adult onset of depression (Sabia, 2003). It is thought that early sexual contact influences depression through remodeling of systems not yet equipped or sufficiently mature to handle this type of social interaction. Identifying mental health problems among adolescent patients who are engaging in sexual intercourse can expand upon current methods of diagnosis in ways that advance the development of new intervention strategies (Anderson & Teicher, 2008). There are benefits of modeling depression in animals as they provide a means of identifying the development of dysfunctional properties, understanding the neural systems involved, and creating appropriate treatment management strategies in early sex exposed animals as they relate to humans (Cryan & Holmes, 2005).
A hamster (Phodopus sungorus) model of first sexual encounter in adolescence was used to test the hypothesis that a salient social interaction, specifically sexual experience, affects adult behavioral responses, modifies immunological function in adulthood, and affects reproductive growth. At birth, male hamsters were randomly assigned to one of five groups: (1) experienced first sexual contact with an ovariectomized, estrogen-primed, adult female during puberty at postnatal day 40 (P40) and underwent behavioral testing on day 120, (2) experienced first sexual contact with an ovariectomized, estrogen-primed, adult female during puberty at postnatal day 40 (P40) and tested through behavioral measures at 80 days of life, (3) first sexual bout with an ovariectomized, estrogen-primed, adult female occurred in adulthood at postnatal day 80 (P80) and underwent behavioral testing on day 120, first sexual bout with an ovariectomized, estrogen-primed, adult female occurred in adulthood at postnatal day 80 (P80) and went through behavioral testing on day 160, or (5) received no sexual contact. The group that experienced first sexual contact at 40days and were tested at 80 days (40X40) and the group that experienced first sexual contact at 80days and were tested at 160 days of life (80 X80) where added through a second installment of the study in order to control for age of animal at the time of testing. The addition of additional groups (40X40) and (80X80) accounted for age discrepancies that may have arisen due to differences in the length of time between the first sexual encounter and the beginning of behavioral testing. Hamsters underwent behavioral testing in the form of the elevated plus maze; (EPM), designed to assess anxiety like responses, the Porsolt forced swim test; (FST) and sucrose anhedonia test; (SA), which are measures of behavioral despair and anhedonia, respectively. Following behavioral tests, cell-mediated immune responses were assessed through the use of delayed type hypersensitivity (DTH). Real-time quantitative polymerase chain reaction (PCR) was used to assess the amount of gene expression of specific cDNA levels of inflammatory markers within the emotion and affect related regions of the brain (i.e., PFC, hippocampus, amygdala, striatum). Blood samples were obtained prior to and following sex to determine glucocorticoid concentrations.
Compared to sexually inexperienced hamsters and hamsters that did not experience sexual interactions until adulthood, hamsters with adolescent sexual experience increased anxiety- and depressive-like behavioral responses. Adolescent sexual experience also markedly increased immune responses, suggesting that premature exposure to sexual encounters may increase cell-mediated immunity as well as influence affective responses in adulthood. Adolescent sexual experiences increased the presence of the pro-inflammatory cytokine interleukin 1β (IL-1β) in the brain, specifically in the prefrontal cortex (PFC). The prefrontal cortex is involved in a range of cognitive and executive functions such as: working memory, attentional set shifting, planned behavior, behavioral inhibition, decision making, and integration of voluntary behavior (Dalley, Cardinal, & Robbins, 2004). Recent experimental observations suggest that brief exposure to stress may be sufficient to induce structural neural reorganization within the PFC and that experience driven morphological alterations to the PFC may be accountable for some symptoms of depression (Holmes & Wellman, 2009). The finding that IL-1β is increased in hamsters experiences sex during adolescence suggests that relevant social stimuli during this sensitive time may increase neuroinflammation and subsequent vulnerability to psychopathologies similar to what past research has shown. These animals also reduced overall body mass and accessory reproductive tissue mass, which may be mediated through IL-1β expression.
Taken together, these results suggest that early adolescent sexual experience has long-term effects on affective responses, enduring effects on adult immune function, as well as lasting effects on reproductive tissue. This work may be useful in understanding the long-term physical and mental health outcomes of adolescent sex in humans.