Adolescent cortical development: A critical period of vulnerability for addiction

doi:10.1016/j.pbb.2006.12.001

Pharmacology Biochemistry and Behavior

Volume 86, Issue 2, February 2007, Pages 189-199

https://doi.org/10.1016/j.pbb.2006.12.001 Get rights and content

Abstract

Cortical growth and remodeling continues from birth through youth and adolescence to stable adult levels changing slowly into senescence. There are critical periods of cortical development when specific experiences drive major synaptic rearrangements and learning that only occur during the critical period. For example, visual cortex is characterized by a critical period of plasticity involved in establishing visual acuity. Adolescence is defined by characteristic behaviors that include high levels of risk taking, exploration, novelty and sensation seeking, social interaction and play behaviors. In addition, adolescence is the final period of development of the adult during which talents, reasoning and complex adult behaviors mature. This maturation of behaviors corresponds with periods of marked changes in neurogenesis, cortical synaptic remodeling, neurotransmitter receptors and transporters, as well as major changes in hormones. Frontal cortical development is later in adolescence and likely contributes to refinement of reasoning, goal and priority setting, impulse control and evaluating long and short term rewards. Adolescent humans have high levels of binge drinking and experimentation with other drugs. This review presents findings supporting adolescence as a critical period of cortical development important for establishing life long adult characteristics that are disrupted by alcohol and drug use.

Section snippets

Introduction: Adolescence; a unique period of development

Adolescence is a critical period of development during the transition from childhood to adulthood. The ages associated with adolescence are commonly considered in humans to be approximately 12 to 20–25 years of age, and postnatal days (PND) 28 to 42 (Spear, 2000) in rodents. Adolescence is best defined by characteristic adolescent behaviors that include high levels of risk-taking, high exploration, novelty and sensation seeking, social interaction, high activity and play behaviors that likely

Adolescent brain remodeling

The adolescent brain is in a unique state of transition as it undergoes both progressive and regressive changes providing a biological basis for the unique adolescent behaviors and the associated changes in behavior during maturation to adulthood. Human magnetic resonance imaging (MRI) studies have demonstrated an inverted U-shape change in the gray matter volume during adolescent period, with a pre-adolescent increase followed by a post-adolescent decrease (Giedd et al., 1999, Giedd, 2004). At

Critical periods of cortical development

Critical periods are specific windows during development when both genetic driven processes and environmental processes, e.g. nature and nurture, interact to establish functional characteristics. These interactions correspond to structural rearrangements of the cerebral cortex that occur during this specific developmental window. As described above, cortical development in humans occurs over the first 3 decades of life with grey matter changes correlating with post-mortem findings of brain

Glutamate and NMDA receptor systems

The binding of cortical glutamate to its NMDA receptor subtype peaks in early adolescence, and declines significantly thereafter, with a loss of one-third of NMDA receptors by PND60 (Insel et al., 1990, Guilarte, 1998). Such synaptic pruning contributes to the loss of excitatory glutamate input to NAc (Frantz and Van Hartesveldt, 1999a) and a reduction in accumbal NMDA receptors (Frantz and Van Hartesveldt, 1999b) during adolescent brain maturation. Interestingly, long-term potentiation (LTP),

Transcription factor CREB and growth factor BDNF in adolescence

The cAMP-response element binding protein (CREB) is an important mediator for the differentiation and maturation of CNS neurons. CREB is also critical for induction of trophic factors such as BDNF, for neuronal vitality and for learning and memory (Bender et al., 2001, Zou and Crews, 2006). Through phosphorylation, CREB is activated to propagate signals from synapses to the nucleus to the expression of genes necessary for synaptic plasticity (Martin and Kandel, 1996, Silva et al., 1998, Bender

Neurogenic processes in adolescent brains

Although neurogenesis is primarily an early developmental process with most neurons being formed in the prenatal and early postnatal periods, it continues into adulthood within specific adult brain regions including the forebrain subventricular zone (SVZ) and hippocampal dentate gyrus (DG) where neurogenesis continues into senescence. Generating and integrating new neurons into preexisting neuronal circuits is believed to enable the hippocampus to adapt to novel and more complex situations (

Adolescent behavior: Risky, motivated, and vulnerable

As just noted, the adolescent brain undergoes remodeling in a variety of structural and functional regions, particularly corticolimbic and frontal regions known to regulate emotional as well as analytical and executive processes. Simultaneous with these changes, adolescents demonstrate new behaviors that are associated with acquisition of adult cognitive and emotional repertoires (Yates, 1996). These are normal adaptive changes that help usher the adolescent into adulthood. However, adolescents

Adolescent alcohol abuse is common

Alcohol use among adolescents is common. As described earlier, adolescent high risk-taking, thrill and novelty-seeking behaviors promote heavy drinking and other drug experimentation. Individuals in their teens and early twenties are among the heaviest episodic drinkers. For example, among U.S. high school students 12% of 8th graders (13–14 years of age), 22% of 10th graders and 28% of 12th grade seniors reported heavy episodic drinking within the past 2 weeks (Johnston et al., 2004). According

Binge drinking during critical periods in cortical development may lead to life long changes of executive function

The effects of alcohol on adolescent brains are different from those on adults. Adolescents are less sensitive to the sedative effects of alcohol (Silveri and Spear, 1998), which allows them to binge drink, however, they are more vulnerable to alcohol-induced neurotoxicity (Monti et al., 2005). The increase in sensitivity of the adolescent brain to toxicity and the dynamic synaptic remodeling of the maturing adolescent brain may enhance the strong learning components of heavy drinking behaviors

Summary

Adolescence represents an important period of brain development, particularly for the cerebral cortex. There are critical periods of development when the cortex is sensitive to environment induced changes in synaptic strength. Between the ages of 10 and 25 years there are major changes in synaptic receptors and density as well as myelination of frontal cortical areas important for impulse control, goal setting, motivation, interpersonal interactions, reasoning, assessment of rewards and

Acknowledgements

This research is supported by NIAAA. We would also like to thank Melissa Mann for manuscript preparation.

References (138)

J. Arnett
Reckless behavior in adolescence: a developmental perspective
Dev Rev
(1992)
O. Bar-Peled et al.
Fetal human brain exhibits a prenatal peak in the density of serotonin 5-HT1A receptors
Neurosci Lett
(1991)
P.W. Burnet et al.
Detection and quantitation of 5-HT1A and 5-HT2A receptor mRNAs in human hippocampus using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and their correlation with binding site densities and age
Neurosci Lett
(1994)
H.A. Cameron et al.
Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus
Neuroscience
(1994)
W.A. Carlezon et al.
The many faces of CREB
Trends Neurosci
(2005)
S. Choi et al.
Control of endogenous norepinephrine release in the hypothalamus of male rats changes over adolescent development
Brain Res Dev Brain Res
(1997)
F.T. Crews et al.
Neurogenesis in adolescent brain is potently inhibited by ethanol
Neuroscience
(2006)
G. Daval et al.
Autoradiographic evidence of serotonin1 binding sites on primary afferent fibres in the dorsal horn of the rat spinal cord
Neurosci Lett
(1987)
E. del Olmo et al.
Early localization of mRNA coding for 5-HT1A receptors in human brain during development
Brain Res Mol Brain Res
(1998)
K.A. Dillon et al.
Autoradiographic analysis of serotonin 5-HT1A receptor binding in the human brain postmortem: effects of age and alcohol
Brain Res
(1991)

A. Dinopoulos et al.

The serotonin innervation of the basal forebrain shows a transient phase during development

Brain Res Dev Brain Res

(1997)

I.E. Dori et al.

The development of the synaptic organization of the serotonergic system differs in brain areas with different functions

Exp Neurol

(1998)

R.S. Duman et al.

Neuronal plasticity and survival in mood disorders

Biol Psychiatry

(2000)

K. Frantz et al.

The locomotor effects of MK801 in the nucleus accumbens of developing and adult rats

Eur J Pharmacol

(1999)

K. Frantz et al.

Locomotion elicited by MK801 in developing and adult rats: temporal, environmental, and gender effects

Eur J Pharmacol

(1999)

H. Golombek et al.

Feeling states during adolescence

Psychiatr Clin North Am

(1990)

E. Gould

Serotonin and hippocampal neurogenesis

Neuropsychopharmacology

(1999)

E. Gould et al.

Postnatal development of cholinergic neurons in the rat: I. Forebrain

Brain Res Bull

(1991)

B.F. Grant et al.

Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey

J Subst Abuse

(1998)

A. Gregus et al.

Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats

Behav Brain Res

(2005)

T. Guilarte

The N-methyl-d-aspartate receptor: physiology and neurotoxicology in the developing brain

Y. Hachiya et al.

Development of GABAergic neurons and their transporter in human temporal cortex

Pediatr Neurol

(2001)

J. He et al.

Neurogenesis Decreases during Brain Maturation from Adolescence to Adulthood

Pharmacol Biochem Behav

(2007)

T.R. Insel et al.

The ontogeny of excitatory amino acid receptors in rat forebrain-I. N-methyl-d-aspartate and quisqualate receptors

Neuroscience

(1990)

J.S. Johnson et al.

Critical period effects in second language learning: the influence of maturational state on the acquisition of English as a second language

Cognit Psychol

(1989)

C.K. Kellogg et al.

Altered stressor-induced changes in GABAA receptor function in the cerebral cortex of adult rats exposed in utero to diazepam

Pharmacol Biochem Behav

(1993)

C.K. Kellogg et al.

Adolescent development alters stressor-induced Fos immunoreactivity in rat brain

Neuroscience

(1998)

J.E. Malberg et al.

Antidepressant action: to the nucleus and beyond

Trends Pharmacol Sci

(2005)

K.C. Martin et al.

Cell adhesion molecules, CREB, and the formation of new synaptic connections

Neuron

(1996)

A.E. Medina et al.

Early alcohol exposure impairs ocular dominance plasticity throughout the critical period

Brain Res Dev Brain Res

(2005)

A.K. Mehta et al.

Effect of chronic administration of ethanol on GABAA receptor assemblies derived from alpha2-, alpha3-, beta2- and gamma2-subunits in the rat cerebral cortex

Brain Res

(2005)

H. Mohler et al.

GABA(A)-receptor subtypes: a new pharmacology

Curr Opin Pharmacol

(2001)

D.A. Morilak et al.

Ontogeny of 5-hydroxytryptamine2 receptor immunoreactivity in the developing rat brain

Neuroscience

(1993)

Y. Munakata et al.

Developmental cognitive neuroscience: progress and potential

Trends Cogn Sci

(2004)

S. Nurse et al.

Late maturation of GABA(B) synaptic transmission in area CA1 of the rat hippocampus

Neuropharmacology

(1999)

J.A. Obernier et al.

Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats

Pharmacol Biochem Behav

(2002)

D.R. Rosenberg et al.

Changes in the dopaminergic innervation of monkey prefrontal cortex during late postnatal development: a tyrosine hydroxylase immunohistochemical study

Biol Psychiatry

(1994)

M.R. Rosenzweig et al.

Psychobiology of plasticity: effects of training and experience on brain and behavior

Behav Brain Res

(1996)

W. Adriani et al.

Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine

Neuropsychopharmacology

(2004)

W. Adriani et al.

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment

Psychopharmacology (Berl)

(2006)

S.L. Andersen et al.

Delayed effects of early stress on hippocampal development

Neuropsychopharmacology

(2004)

S.L. Andersen et al.

Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats

Synapse

(2000)

G.L. Andrucci et al.

The relationship of MMPI and Sensation Seeking Scales to adolescent drug use

J Pers Assess

(1989)

D. Baumrind

A developmental perspective on adolescent rick taking in contemporary America

R.A. Bender et al.

Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation

Eur J Neurosci

(2001)

T.J. Berndt

Developmental changes in conformity to peers and parents

Dev Psychol

(1979)

A. Biglan et al.

Social and behavioral factors associated with high-risk sexual behavior among adolescents

J Behav Med

(1990)

S.J. Blakemore et al.

Development of the adolescent brain: implications for executive function and social cognition

J Child Psychol Psychiatry

(2006)

A.R. Brooks-Kayal et al.

gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development

J Neurochem

(2001)

B.J. Casey et al.

A pediatric functional MRI study of prefrontal activation during performance of a Go-No-Go task

J Cogn Neurosci

(1997)

Cited by (781)

Adolescent nicotine exposure promotes adulthood opioid consumption that persists despite adverse consequences and increases the density of insular perineuronal nets
2024, Addiction Neuroscience
Adolescence marks a sensitive period for neurodevelopment wherein exposure to drugs of abuse may disrupt maturation and induce persistent changes in neurophysiology which may exacerbate the risk for developing substance use disorders in adulthood. Adolescent nicotine exposure (ANE) enhances motivation to obtain drugs of abuse, particularly opioids, and increases vulnerability for the development of opioid use disorder (OUD). Here, we characterized ANE effects on learning about the adverse consequences of opioid consumption in adulthood in the absence of further nicotine administration. First, we show that ANE engenders punishment resistant fentanyl self-administration in a heterogenous seeking–taking chain schedule of reinforcement at least at the tested dose of fentanyl (0.75 µg/kg). We found that ANE rats consumed significantly more fentanyl and contingent foot shock punishment was less efficacious in limiting fentanyl seeking in ANE rats, relative to nicotine-naïve controls. Next, we demonstrated that ANE limits learning about the deleterious consequences of acute opioid intoxication in adulthood. In a combined conditioned taste avoidance and place preference paradigm we found that ANE resulted in significant reductions in the strength of morphine-induced CTA, and a simultaneous enhancement of CPP at a higher dose that was less capable of driving reinforcement in naïve controls. Finally, we examined the expression of perineuronal nets (PNNs) within insular cortex (IC) and found ANE rats to have increased density of PNNs across the anterior IC and significantly more parvalbumin-labeled IC cells relative to naïve controls. Together, these data lay the framework for a mechanistic explanation of the extreme comorbidity between nicotine use and development of OUDs.
Does cannabis affect cognitive functioning in patients with schizophrenia?
2024, Schizophrenia Research: Cognition
Cannabis use impairs cognitive performance in healthy subjects; several studies have shown improved cognitive outcomes in schizophrenic patients using cannabis. The aim of this study was to evaluate the effects of cannabis use on cognitive function in Moroccan patients with schizophrenia who were cannabis users.
Two groups were recruited in a Moroccan University Psychiatric Centre. Fifty patients diagnosed with schizophrenia according to the DSM-V who were cannabis users (SZ CANN +) and forty-nine patients diagnosed with schizophrenia according to DSM-V who do not use cannabis (SZ CANN-). Cognitive functioning was assessed using the CogState neuropsychological battery.
The results of the study suggest that SZ CANN- patients performed better in the test of psychomotor function, attention and verbal memory. While SZ CANN+ patients performed better in the test of working memory, visual memory and emotional recognition. We found no relationship between SZ CANN+ patients and SZ CANN- patients concerning executive function.
Our results suggest that cannabis use may have different effects on neurocognitive functioning. It is associated with disorders of psychomotor function, attention and verbal memory. So, it is associated with an improvement in working memory, visual memory and emotion recognition.
Stress inoculation during adolescence attenuates social stress-induced increase in ethanol intake in adult male mice
2024, Neuropharmacology
Social stress exposure heightens the risk of substance abuse disorder development, especially when endured during adolescence, influencing long-term mental health. This study investigates early-life stress's potential to confer resilience against later-life stressors. To investigate this hypothesis, we examined the impact of a single social defeat (SD) incident during adolescent mice's lives on subsequent voluntary ethanol consumption following repeated adult social stress exposure. Half of the adolescent mice experienced SD at postnatal day 28. Three weeks later (postnatal day 49), defeated groups encountered four confrontations with aggressive residents every 72 h, while control groups were exposed to non-resident exploration. A day after the last SD, defeated mice were classified as resilient or susceptible based on their response to a social interaction test (SIT), a model for depressive behavior. To assess ethanol consumption during young adulthood, researchers used the ‘drinking in the dark’ and oral ethanol self-administration paradigms. Stress inoculation (IS) slightly increased resilient animals in the SIT. In mice without IS exposure during adolescence, susceptible defeated mice displayed higher ethanol consumption and motivation than control and resilient mice. IS in adolescence effectively counteracted this effect, as IS-SD groups, whether resilient or susceptible, showed no increase in ethanol intake. These groups also exhibited similar motivation to control, measured by the progressive ratio. Notably, elevated IL-6 levels seen in SD-S mice were absent in IS-exposed mice. Additionally, IS-exposed groups had lower prefrontal cortex IL-6 and CX3CL1 levels. These findings support the hypothesis that IS, induced by moderate-intensity stress during adolescence, can enhance resilience to more severe stressors in adulthood.
Differential consumption of alcohol, caffeine, and caffeinated alcohol by adolescent rats, and effects on post-adolescent gene expression signatures in the nucleus accumbens and orbitofrontal cortex
2023, Drug and Alcohol Dependence
Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.03%), alcohol (10%), caffeinated alcohol (0.03% + 10%), or vehicle and evaluated the effects of this on mRNA expression in brain regions associated with addiction and known to be affected by each drug. Beginning on postnatal day 30, rats were allowed unrestricted access to gelatin combined with one, both, or neither drug for twenty days. Compared to vehicle-consuming animals, consumption of gelatin was significantly attenuated when alcohol was included. The addition of caffeine to alcohol increased alcohol consumption in the early days of access compared to alcohol alone; however, after two weeks, alcohol consumption between these groups reached comparable levels. Compared to animals consuming caffeine alone, combining caffeine with alcohol significantly reduced caffeine intake. Targeted mRNA analysis of tissue collected from the nucleus accumbens and orbitofrontal cortex after the consumption period identified unique patterns of differentially expressed genes between treatment groups, across a broad array of neurotransmitter systems. Of particular note were genes related to a number of solute transporters and serotonergic functions. This preliminary work suggests unique pharmacological and behavioral effects from consuming caffeinated alcohol during adolescence. Since CABs are widely consumed by adolescents, these results suggest that more research into the pharmacological and behavioral effects elicited by CABs is warranted.
The interconnection between obesity and executive function in adolescence: The role of the gut microbiome
2023, Neuroscience and Biobehavioral Reviews
In the United States, adolescent obesity is a growing epidemic associated with maladaptive executive functioning. Likewise, data link the microbiome to obesity. Emerging microbiome research has demonstrated an interconnection between the gut microbiome and the brain, indicating a bidirectional communication system within the gut–microbiome–brain axis in the pathophysiology of obesity. This narrative review identifies and summarizes relevant research connecting adolescent obesity as it relates to three core domains of executive functioning and the contribution of the gut microbiome in the relationship between obesity and executive functions in adolescence. The review suggests that (1) the interconnection between obesity, executive function, and the gut microbiome is a bidirectional connection, and (2) the gut microbiome may mediate the neurobiological pathways between obesity and executive function deficits. The findings of this review provide valuable insights into obesity-associated executive function deficits and elucidate the possible mediation role of the gut microbiome.
Adolescent user behaviors on short video application, cognitive functioning and academic performance
2023, Computers and Education
Despite the soaring popularity of short video application (SVA) worldwide and its unique affordances provided for adolescent development, little is known about its potential impact on adolescent users' cognitive ability. This study aimed to examine whether and how adolescents’ user behaviors regarding SVA, including daily usage and reliance on algorithmic recommendations, predict their cognitive functioning and academic performance. A sample of Chinese adolescents from two age cohorts (M_age = 12.25, SD = 0.02, N = 454; M_age = 15.21, SD = 0.02, N = 368) completed the survey on SVA user behavior and cognitive ability tests regarding academic delay of gratification (ADOG), working memory and verbal ability, with their academic performance assessed by final exam grades. The findings reveal that daily usage of SVA predicted lower ADOG and academic performance for both age cohorts. SVA daily usage also predicted lower working memory and verbal ability for the younger cohort only, which simultaneously mediated the associations between their user behaviors and poorer academic performance. And the dependency on algorithmic personalization predicted lower working memory for the younger cohort only. Regarding the age differences in SVA-related effects, the study further points out the higher susceptibility of younger adolescents to SVA use compared to their older counterparts, which should be noted by students, parents, educators and researchers so as to prevent the potentially negative impact of using SVA.

View all citing articles on Scopus

View full text

ReviewAdolescent cortical development: A critical period of vulnerability for addiction

Abstract

Section snippets

Introduction: Adolescence; a unique period of development

Adolescent brain remodeling

Critical periods of cortical development

Glutamate and NMDA receptor systems

Transcription factor CREB and growth factor BDNF in adolescence

Neurogenic processes in adolescent brains

Adolescent behavior: Risky, motivated, and vulnerable

Adolescent alcohol abuse is common

Binge drinking during critical periods in cortical development may lead to life long changes of executive function

Summary

Acknowledgements

Dev Rev

Neurosci Lett

Neurosci Lett

Neuroscience

Trends Neurosci

Brain Res Dev Brain Res

Neuroscience

Neurosci Lett

Brain Res Mol Brain Res

Brain Res

Brain Res Dev Brain Res

Exp Neurol

Biol Psychiatry

Eur J Pharmacol

Eur J Pharmacol

Psychiatr Clin North Am

Neuropsychopharmacology

Brain Res Bull

J Subst Abuse

Behav Brain Res

Pediatr Neurol

Pharmacol Biochem Behav

Neuroscience

Cognit Psychol

Pharmacol Biochem Behav

Neuroscience

Trends Pharmacol Sci

Neuron

Brain Res Dev Brain Res

Brain Res

Curr Opin Pharmacol

Neuroscience

Trends Cogn Sci

Neuropharmacology

Pharmacol Biochem Behav

Biol Psychiatry

Behav Brain Res

Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine

Neuropsychopharmacology

Response to novelty, social and self-control behaviors, in rats exposed to neonatal anoxia: modulatory effects of an enriched environment

Psychopharmacology (Berl)

Delayed effects of early stress on hippocampal development

Neuropsychopharmacology

Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats

Synapse

The relationship of MMPI and Sensation Seeking Scales to adolescent drug use

J Pers Assess

A developmental perspective on adolescent rick taking in contemporary America

Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation

Eur J Neurosci

Developmental changes in conformity to peers and parents

Dev Psychol

Social and behavioral factors associated with high-risk sexual behavior among adolescents

J Behav Med

Development of the adolescent brain: implications for executive function and social cognition

J Child Psychol Psychiatry

gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development

J Neurochem

A pediatric functional MRI study of prefrontal activation during performance of a Go-No-Go task

J Cogn Neurosci

Review
Adolescent cortical development: A critical period of vulnerability for addiction