Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence

Laviola, Giovanni; Macrı̀, Simone; Morley‐Fletcher, Sara; Adriani, Walter

doi:10.1016/s0149-7634(03)00006-x

Cited by 547 publications

(384 citation statements)

References 115 publications

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“…However, other studies have found relatively greater novel environment locomotor exploration in adolescent CD-1 mice [1,29], while studies in rats report both normal and greater open field locomotion in adolescents relative to adults [14,16,17,35,36,46]. Some authors have proposed that differences in locomotor exploration between adolescents and adults are related to the extent that novelty drives behavior in a given test situation and this factor may account for the apparent discrepancies across studies [30]. Notwithstanding, levels of locomotor activity in adolescent mice in the current study are unlikely to account for the relatively higher levels of active swimming behavior exhibited by adolescent mice in the forced swim test for depression-related behavior.…”

Section: Discussionmentioning

confidence: 98%

“…Depression-related behavior was also tested using a pharmacologically-validated test, the forced swim test [11]. The subjects employed for this study were C57BL/6J mice, aged four, six or eight weeks considered to approximate to human early adolescence, peri-adolescence and early adulthood, respectively [12,30,45]. The C57BL/6J inbred strain was chosen on the basis of its widespread use in behavioral neuroscience research and its inclusion as a 'group A' priority strain in the Mouse Phenome Project; an international effort to provide the biomedical research community with phenotypic data on the most commonly used mouse strains (http://aretha.jax.org/pubcgi/phenome/mpdcgi?rtn=docs/home).…”

Section: Introductionmentioning

confidence: 99%

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Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Hefner¹,

Holmes²

2007

Behavioural Brain Research

167

123

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Adolescence is characterized by behavioral traits such as emotional lability and impulsivity that are associated with increased vulnerability to affective illness and addictions. Research in rodents has found that adolescent rats and mice differ from adults on measures of anxiety-like behavior, noveltyseeking and stress-responsivity. The present study sought to extend these data by evaluating fear-, anxiety-and depression-related behaviors in male C57BL/6J mice aged four (early adolescent), six (peri-adolescent) or eight (early adult) weeks of age. Age-groups were compared on: Pavlovian fear conditioning and extinction, anxiety-like behavior and exploratory locomotion (using elevated plusmaze and novel open field), and depression-related behavior (via forced swim test). Results showed that early adolescent mice exhibited enhanced fear conditioning, but extinguished at a similar rate as adults. There were no major differences in anxiety-like behavior across age-groups, although early adolescent and peri-adolescent mice exhibited less exploratory locomotion than adults. Depressionrelated immobility behavior in the forced swim test was lower in early adolescents than adult mice across three test exposures. Present findings in the C57BL/6J inbred strain add to growing evidence of changes in rodent fear-and stress-related behaviors across the developmental transition from juvenility through adulthood. Understanding the neural basis of these ontogenic changes could provide insight into factors could provide insight into the pathogenesis and treatment of affective disorders that have their origins in adolescence.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Hefner¹,

Holmes²

2007

Behavioural Brain Research

167

123

View full text Add to dashboard Cite

show abstract

“…As in our previous work, in this study, we define 'early adolescence' in C57BL/6 mice as the period between the day of weaning and PND 32. These definitions seem now to be a consensus in the mouse literature (eg, (Spear, 2000;Laviola et al, 2003;Schneider, 2013;Tirelli et al, 2003). This is not an absolute margin, but rather an age range during which mice exhibit distinct neurobehavioral characteristics.…”

Section: Experimental Procedures and Timelinementioning

confidence: 99%

Amphetamine in Adolescence Disrupts the Development of Medial Prefrontal Cortex Dopamine Connectivity in a dcc-Dependent Manner

Reynolds

Makowski

Yogendran

et al. 2014

Neuropsychopharmacol

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Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifetime. Intriguingly, adolescence is a period of dynamic refinement in the organization of neuronal connectivity, in particular medial prefrontal cortex (mPFC) dopamine circuitry. The guidance cue receptor, DCC (deleted in colorectal cancer), is highly expressed by dopamine neurons and orchestrates their innervation to the mPFC during adolescence. Furthermore, we have shown that amphetamine in adolescence regulates DCC expression in dopamine neurons. Drugs in adolescence may therefore induce their enduring behavioral effects via DCC-mediated disruption in mPFC dopamine development. In this study, we investigated the impact of repeated exposure to amphetamine during adolescence on both the development of mPFC dopamine connectivity and on salience attribution to drug context in adulthood. We compare these effects to those induced by adult exposure to an identical amphetamine regimen. Finally, we determine whether DCC signaling within dopamine neurons is necessary for these events. Exposure to amphetamine in adolescence, but not in adulthood, leads to an increase in the span of dopamine innervation to the mPFC, but a reduction of presynaptic sites present on these axons. Amphetamine treatment in adolescence, but not in adulthood, also produces an increase in salience attribution to a previously drug-paired context in adulthood. Remarkably, DCC signaling within dopamine neurons is required for both of these effects. Drugs of abuse in adolescence may therefore induce their detrimental behavioral consequences by disrupting mesocortical dopamine development through alterations in the DCC signaling cascade.

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“…These peculiar novelty-seeking and impulsive traits are transiently expressed during the phase of adolescence (Arnett, 1992;Laviola et al, 2003), but in some vulnerable individuals can then be maintained at adult ages, leading to extreme (borderline, if not pathological) behaviors like e.g. drug misuse, exaggerate sexual activity, reckless driving, and also PG (Zuckerman and Kuhlman, 2000).…”

Section: Impulsivity and Novelty Seekingmentioning

confidence: 99%

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

et al. 2009

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Abstract-Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999 -1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/ silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/ delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attentiondeficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

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Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence

Cited by 547 publications

References 115 publications

Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Amphetamine in Adolescence Disrupts the Development of Medial Prefrontal Cortex Dopamine Connectivity in a dcc-Dependent Manner

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

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