Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models (original) (raw)
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In humans, experimentation with drugs (including alcohol) typically begins in adolescence. Adolescent experimentation can escalate to abuse and dependence in adulthood. Converging evidence from molecular, cellular and systems analyses demonstrate adolescence as a plastic period of brain development when important modifications occur in reward pathway signaling. Environmental factors, including exposure to drugs, have the potential to impact these critical neurodevelopmental changes. Rodent models offer well-controlled and cost-effective methods of assessing neurobiological and longitudinal effects. This paper reviews research on drug self-administration during adolescence and subsequent propensity for abuse in adulthood as determined by rodent models. Self-administration studies report increased drug intake in adolescent rats, independent of changes in ingestive behavior. Some longitudinal studies report that adolescent drug use leads to increased consumption during adulthood, but r...
Enhanced behavioral response to related-dose cocaine in adolescent rats
Psychopharmacology, 2006
Rationale: Most lifelong drug addiction in humans originates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. Objectives: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. Results: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine blood and brain levels were not significantly different between age groups during any of the exposure sessions. Conclusions: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.
Enhanced behavioral response to repeated-dose cocaine in adolescent rats
2005
Rationale: Most lifelong drug addiction in humans originates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. Objectives: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. Results: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine blood and brain levels were not significantly different between age groups during any of the exposure sessions. Conclusions: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.
Brain and Cognition, 2010
Adolescence is an evolutionarily conserved developmental phase characterized by hormonal, physiological, neural and behavioral alterations evident widely across mammalian species. For instance, adolescent rats, like their human counterparts, exhibit elevations in peer-directed social interactions, risk-taking/novelty seeking and drug and alcohol use relative to adults, along with notable changes in motivational and reward-related brain regions. After reviewing these topics, the present paper discusses conditioned preference and aversion data showing adolescents to be more sensitive than adults to positive rewarding properties of various drugs and natural stimuli, while less sensitive to the aversive properties of these stimuli. Additional experiments designed to parse specific components of reward-related processing using natural rewards have yielded more mixed findings, with reports of accentuated positive hedonic sensitivity during adolescence contrasting with studies showing less positive hedonic affect and reduced incentive salience at this age. Implications of these findings for adolescent substance abuse will be discussed.
Role of individual and developmental differences in voluntary cocaine intake in rats
Psychopharmacology, 2011
Rationale-Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addictionlike behavior and to examine factors that promote self-administration. Methods-We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task.
Psychopharmacology, 2020
Rationale: Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared to adults; however, the contribution of adolescent-formed context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced cocaine-seeking during adolescence vs adulthood is unknown. Objectives: The present study compared the effect of adolescent vs adult-formed context-drug associations under differential housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified, abbreviated (ABRV) paradigm. Methods: In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2 hr, 1x/day, 10 days), extinction training (EXT) in a second context (1 hr, 1x/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2-3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2 hr, 2x/day, 5 days), EXT (1 hr, 4x/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions. Results & Conclusions: Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under Non-ABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence.
Neurobiology of the Adolescent Brain and Behavior: Implications for Substance Use Disorders
2010
Adolescence is a developmental period that entails substantial changes in risktaking behavior and experimentation with alcohol and drugs. Understanding how the brain is changing during this period relative to childhood and adulthood and how these changes vary across individuals are key in predicting risk for later substance abuse and dependence. Method: This review discusses recent human imaging and animal work in the context of an emerging view of adolescence as characterized by a tension between early emerging "bottom-up" systems that express exaggerated reactivity to motivational stimuli and later maturing "top-down" cognitive control regions. Behavioral, clinical, and neurobiological evidences are reported for dissociating these two systems developmentally. The literature on the effects of alcohol and its rewarding properties in the brain is discussed in the context of these two systems. Results: Collectively, these studies show curvilinear development of motivational behavior and the underlying subcortical brain regions, with a peak inflection from 13 to 17 years. In contrast, prefrontal regions, important in top-down regulation of behavior, show a linear pattern of development well into young adulthood that parallels that seen in behavioral studies of impulsivity. Conclusions: The tension or imbalance between these developing systems during adolescence may lead to cognitive control processes being more vulnerable to incentive-based modulation and increased susceptibility to the motivational properties of alcohol and drugs. As such, behavior challenges that require cognitive control in the face of appetitive cues may serve as useful biobehavioral markers for predicting which teens may be at greater risk for alcohol and substance dependence.
RATIONALE: Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated. OBJECTIVE: Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking. METHODS: Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratios schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08 or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf). RESULTS: We found that adult-onset rats acquired METH self-administration more readily and exhi...
International Journal of Developmental Neuroscience, 2004
Cigarette smoking by adolescents is a strong predictor of future drug use, abuse, and dependence. While this "gateway drug effect" is assumed to be related to psychosocial factors, data from our laboratory suggests that adolescent nicotine use may permanently disrupt reward systems through changes in dopamine receptor function. Behavioral pharmacological methods known to be indirectly (motor activity) and directly (conditioned-place-preference) related to drug reinforcement were used to examine changes in cocaine sensitivity. Testing was performed on adult mice that were exposed to nicotine (0.3, 1.0, and 3.0 mg/kg, SC, M-F, b.i.d.) or saline during adolescence (postnatal days 25-57). Prior to testing, subjects had a 28 day drug-free, time-off period. After acclimation to the testing apparatus, the locomotor effects (30 min, 30 cm traveled) of cocaine (5, 10, and 20 mg/kg, IP) were measured daily; cocaine tests were preceded and followed by saline control tests. Following the acute dose-response curve, mice received saline followed by 5 days of 20.0 mg/kg cocaine. Thereafter, mice underwent condition-place-preference testing. A pre-test was performed to determine compartment preference (i.e., no injection, 20 min test). Cocaine (10 mg/kg, IP) was paired with the subjects non-preferred side and saline with the other. Conditioning sessions were conducted for 8 days with the order of drug/saline injections counter-balanced across subjects. A drug-free, post-test occurred on the day following the final conditioning session. A dose-dependent relationship between adolescent nicotine exposure and cocaine reward was noted in the adult mice across both test conditions. Subjects exposed to nicotine showed an increased response to cocaine's motor activating effects and a decreased response to cocaine's rewarding effects. A follow-up study was undertaken to evaluate dopamine D1, D2, and D3 receptor function in adult mice exposed to the highest dose of nicotine from the first study. While both interesting and revealing, the results of motor activity tests with dopamine agonist only approached significance. Further research will be required to more fully examine the mechanism of action for the observed changes in cocaine reward. In summary, this is the first study to demonstrate a dose-response relationship between adolescent nicotine exposure and changes in cocaine reward and sensitivity during adulthood.
The effects of abused drugs on adolescent development of corticolimbic circuitry and behavior
Neuroscience, 2013
Adolescence is a period of significant neurobiological change that occurs as individuals transition from childhood to adulthood. Because the nervous system is in a relatively labile state during this stage of development, it may be especially sensitive to experience-induced plasticity. One such experience that is relatively common to adolescents is the exposure to drugs of abuse, particularly alcohol and psychostimulants. In this review, we highlight recent findings on the long-lasting effects of exposure to these drugs during adolescence in humans as well as in animal models. Whenever possible, our focus is on studies that use comparison groups of adolescent-and adult-exposed subjects as this is a more direct test of the hypothesis that adolescence represents a period of enhanced vulnerability to the effects of drug-induced plasticity. Lastly, we suggest areas of future investigation that are needed and methodological concerns that should be addressed.