Delayed extinction and stronger reinstatement of cocaine conditioned place preference in adolescent rats, compared to adults.

Abstract

Adolescence is a transitional period during development that is associated with a greater likelihood of addiction to drugs than any other age. One possibility for this observation is that learned associations between the rewarding experience of drugs and drug-related cues may produce greater motivational salience, and thus are more difficult to extinguish. Using an unbiased placeconditioning paradigm with two doses of cocaine (10 mg/kg or 20 mg/kg), the authors show here that adolescents require 75 ± 17% more extinction trials than adults to extinguish cocaine placepreferences. Furthermore, once extinguished, adolescents display a greater preference for a previously cocaine-paired environment upon drug-primed reinstatement compared with adults. These results suggest that adolescent vulnerability to addiction involves robust memories for drugassociated cues that are difficult to extinguish. Therefore, drug-addicted adolescents may have a higher risk of relapse than adults, leading to greater prevalence of addiction in this population.

Transient D1Dopamine Receptor Expression on Prefrontal Cortex Projection Neurons: Relationship to Enhanced Motivational Salience of Drug Cues in Adolescence

“…For example, handling is one such variable to consider. Handling history may account for enhanced preferences for lower doses of cocaine, as suggested by comparisons across several studies with and without previous handling (Andersen et al, 2002b;Aberg et al, 2007;Brenhouse and Andersen, 2008). Together, age-related differences in the place-conditioning effects of cocaine reported here are consistent with an enhanced sensitivity to these effects in adolescent rats, when examining male animals in an unbiased place-conditioning paradigm.…”

“…This is consistent with the notion that adolescence is characterized by a high sensitivity to reward (Chambers et al, 2003;Tirelli et al, 2003;Ernst et al, 2006), although this sensitivity may partly be caused by enhanced cortical drive as suggested here. Adolescents also maintain context-drug associations 75% longer than adults during extinction of cocaineconditioned place preferences and demonstrate stronger drug-primed reinstatement (Brenhouse and Andersen, 2008). Together, these data suggest greater salience attribution to cocaine-paired cues during adolescence.…”

“…The assessment of motivational responsiveness to stimulants during development is not well defined in the literature for a number of reasons. Inconsistencies in paradigms used, handling stressors, ages, sex (Campbell et al, 2000), drug doses, and the use of stimulants with different behavioral sequelae, such as stereotypy, yield variable conclusions, ranging from decreased amphetamine place conditioning to a heightened sensitivity to cocaine place conditioning in adolescence (Campbell et al, 2000;Tirelli et al, 2003;Badanich et al, 2006;Balda et al, 2006;Schramm-Sapyta et al, 2006) (for review, see Brenhouse and Andersen, 2008). For example, handling is one such variable to consider.…”

Adolescent rats fail to demonstrate a LiCl-induced pre-exposure effect: Implications for the balance of drug reward and aversion in adolescence

“…As noted, adolescents display weaker taste avoidance conditioning in general, and this, too, could be a function of poorer learning in this group. Although possible, adolescents actually display greater drug-induced place preferences (see Badanich et al, 2006;Belluzzi et al, 2004;Brenhouse & Andersen, 2008;Douglas et al, 2003;Torres et al, 2008;Vastola et al, 2002;Zakharova et al, 2009), suggesting that learning in general is not impaired in adolescents. While it is possible that there is a selective learning deficit associated with aversive conditioning (including taste avoidance learning), classic fear conditioning work predicated upon contextual learning suggests that age does not influence the acquisition or extinction of conditioning (Denenberg & Kline, 1958;Kirby, 1963), Interestingly, the retention of such avoidance responses does display a U-shaped function of age (Denenberg & Kline, 1958;Kirby, 1963;Campbell & Campbell, 1962), suggesting that retention of such learning is age dependent.…”

Dopamine D₁-D₂ Receptor Heteromer Regulates Signaling Cascades Involved in Addiction: Potential Relevance to Adolescent Drug Susceptibility

“…Symptoms of depression and schizophrenia, for example, show significant increases during adolescence [5,6] and this developmental period is also associated with an increase in sensitivity to psychostimulant-induced reward [7,8,9,10,11,12,13], placing adolescents at increased risk for the development of drug addiction.…”