Adolescent Alcohol and Stress Exposure Rewires Key Cortical Neurocircuitry

Abstract

Human adolescence is a period of development characterized by wide ranging emotions and behavioral risk taking, including binge drinking (Konrad et al., 2013). These behavioral manifestations of adolescence are complemented by growth in the neuroarchitecture of the brain, including synaptic pruning (Spear, 2013) and increases in overall white matter volume (Perrin et al., 2008). During this period of profound physiological maturation, the adolescent brain has a unique vulnerability to negative perturbations. Alcohol consumption and stress exposure, both of which are heightened during adolescence, can individually and synergistically alter these neurodevelopmental trajectories in positive and negative ways (conferring both resiliency and susceptibility) and influence already changing neurotransmitter systems and circuits. Importantly, the literature is rapidly changing and evolving in our understanding of basal sex differences in the brain, as well as the interaction between biological sex and life experiences. The animal literature provides the distinctive opportunity to explore sex-specific stress- and alcohol- induced changes in neurocircuits on a relatively rapid time scale. In addition, animal models allow for the investigation of individual neurons and signaling molecules otherwise inaccessible in the human brain. Here, we review the human and rodent literature with a focus on cortical development, neurotransmitters, peptides, and steroids, to characterize the field’s current understanding of the interaction between adolescence, biological sex, and exposure to stress and alcohol.

Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice

“…Adolescence is broadly defined as the transitional period between childhood and adulthood, marked by a variety of maturational changes throughout the body (Spear 2000). In the brain, the prefrontal cortex (PFC) is one of the last regions to finalize development, with a variety of morphological, functional, and neuromodulatory changes occurring throughout this period (Sicher et al, 2022). This critical and time-locked development may make the PFC a particularly vulnerable brain region to insults including alcohol use, as any events which interfere with typical PFC development may produce permanent and lifelong consequences.…”

“…While acute risks include car accidents or alcohol poisoning, long-term consequences can include impaired development of the PFC. Studies in both rodent models and human adolescents have shown that alcohol consumption interferes with typical maturation of the prelimbic (PL) region of the PFC, potentially inducing permanent changes in PFC structure and corresponding behavioral aberrations (for review see Sicher et al, 2022). The effects of alcohol on the PL cortex seem to be age dependent, as alcohol consumption during early adolescence, but not early adulthood, increased the excitability of deep-layer cortical pyramidal neurons (Galaj et al, 2020).…”

Adolescent alcohol exposure alters threat avoidance in adulthood

“…Of particular concern are the potential long-term consequences of adolescent binge drinking on brain development. For example, increasing evidence from preclinical models demonstrates that a history of binge-like alcohol exposure during adolescence can lead to persistent changes in cognitive function in adulthood (Spear, 2018 ; Crews et al, 2019 ; Lees et al, 2020 ; Salmanzadeh et al, 2020 ; Sicher et al, 2022 ).…”

Voluntary alcohol consumption during distinct phases of adolescence differentially alters adult fear acquisition, extinction and renewal in male and female rats

“…Alcohol is the most widely abused substance during adolescence, whether due to impulse, sensation seeking, social facilitation, or attempts to cope with the stress of this particular period of life (Bava and Tapert, 2010). Alcohol consumption rates remained high leading up to the COVID-19 pandemic, with over 4.2 million adolescents between the ages of 14 and 20 reporting binge consumption at least once in the month prior (Sicher et al, 2022). Alcohol exposure in adolescence can impart age-dependent, brain-related changes that present in adulthood as reduced resilience to stress-related neuropsychiatric dysfunction (Grant and Harford, 1995, Rohde et al, 2001, Bava and Tapert, 2010; Spear, 2018, Kyzar et al, 2016; Rohde et al, 1996).…”

“…Conversely, impoverished upbringing, poor familial/social support, and toxic environmental exposures can promote developmental trajectories that instead bias individuals towards inflexible and potentially maladaptive behaviors in response to stress and adversity later in life (Silbereis et al, 2016). Accordingly, adolescence is thought to be a particularly vulnerable period when exposure to stress, alcohol, or drugs of abuse disrupts brain development in ways that substantially increase the risk of developing stress-related disorders in adulthood, including posttraumatic stress disorder (PTSD), major depressive disorder, and substance use disorder (Fuhrmann et al, 2015; Sicher et al, 2022).…”