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Review
. 2014 Apr;231(8):1557-80.
doi: 10.1007/s00213-013-3369-1. Epub 2013 Dec 27.

Stress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis

Andrew R Burke  1 , Klaus A Miczek
Affiliations
Review

Stress in adolescence and drugs of abuse in rodent models: role of dopamine, CRF, and HPA axis

Andrew R Burke et al. Psychopharmacology (Berl). 2014 Apr.

Abstract

Rationale: Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction-related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse.

Objectives: Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic-pituitary-adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms.

Results and conclusions: Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Number of publications since 1968 on the topic “adolescence and drugs of abuse” (white bars) and “adolescence and drugs of abuse and stress” (black bars). Scopus.com search1 suggest an 8-fold increase in articles published from 1997 to 2011 on adolescence and the most abused drugs. What has received relatively less attention is the effect of stress on adolescent drug abuse. In fact, adding “stress” to these search criteria reduced the search results by 7-fold (black bars). Footnote: 1Searches conducted at www.scopus.com (Elsevier B.V.) and data were downloaded on June 3rd, 2013. Search terms entered into the field for “Adolescent + Drugs of Abuse” were, “TITLE-ABS-KEY(((rat OR mouse OR monkey OR hamster OR animal) AND (juvenile OR adolescence) AND (cocaine OR heroin OR morphine OR amphetamine OR methamphetamine OR marijuana OR thc OR alcohol OR mdma OR nicotine)))”. Search terms for “Adolescence + Drugs of Abuse + Stress” were, “TITLE-ABS-KEY(((rat OR mouse OR monkey OR hamster OR animal) AND (juvenile OR adolescence) AND (cocaine OR heroin OR morphine OR amphetamine OR methamphetamine OR marijuana OR thc OR alcohol OR mdma OR nicotine) AND stress))”.
Figure 2
Figure 2
Schematic of adolescence and adolescent maturation of behavior (A), hypothalamic pituitary axis (B), and mesocorticoaccumbal dopamine system (C). The lines estimate the relative changes during adolescent development based on the references cited. To improve the accuracy of the ontogenic estimates, only studies that analyzed the dependent variable at more than two time points during adolescence were included in the creation of the lines (see text for details and further citations). (A) Estimated adolescent ontogeny of novelty seeking, play fighting, and contextual freezing behaviors for males (intermittent dashed black line) and females (solid gray line). (B) Estimated ontogeny of the hormones corticosterone (dashed gray line) and adrenocorticotrophic hormone (rough black line) in response to restraint stress during adolescence. (C) Estimated ontogeny of dopamine fibers, dopamine activity, and dopamine receptors for the striatum (dashed black line), nucleus accumbens (rough gray line) and prefrontal cortex (solid black line). References: [1] Vetter-O’Hagen and Spear 2012b; [2] Bolles and Woods 1964; [3] Meaney and Stewart 1981; [4] Pellis and Pellis 1990; [5] Schiffino et al. 2011; [6] Akers et al. 2012; [7] Foilb et al. 2011; [8] Naniex et al. 2012; [9] Tarazi et al. 1998a; [10] Andersen et al. 1997a; [11] Teicher et al. 1993; [12] Andersen and Gazzara 1993; [13] Leslie et al. 1991; [14] Badanich et al. 2006; [15] Andersen et al. 2000; [16] Tarazi and Baldessarini 2000; [17] Tarazi et al. 1998b; [18] Tarazi et al. 1999.
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