Environmental enrichment as a potential intervention for heroin seeking

Galaj, Ewa; Manuszak, M.; Ranaldi, Robert

doi:10.1016/j.drugalcdep.2016.04.016

Cited by 30 publications

(23 citation statements)

References 71 publications

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“…Present results are in agreement with previous reports showing that EE ameliorates EtOH consumption and preference in a 2BC paradigm in mice (Bahi, 2017b ) and counteracts high binge-like EtOH intake triggered by chronic social isolation during early development as well (Lopez and Laber, 2015 ). Also, the present data supports previous studies showing the therapeutic impact of enrichment conditions on drug addiction such as heroin (Galaj et al, 2016 ), methamphetamine (Hajheidari et al, 2015 , 2017 ), and cocaine (Solinas et al, 2008 ; Chauvet et al, 2009 , 2011 , 2012 ; Thiel et al, 2009 ). Future studies extending total time of testing are needed to further explore the temporal dynamic of the beneficial therapeutic impact of EE exposure on binge EtOH intake during adulthood.…”

Section: Discussionsupporting

confidence: 91%

“…To date, the underlying neurobehavioral mechanisms by which EE exerts both a protective and a therapeutic effect on drug and EtOH intake remain unclear, but long-term plastic adaptations in the reward and the stress neurobiological systems have been proposed. Thus, the impact of EE on heroin- and cocaine-seeking behavior and relapse might involve changes in mesocorticolimbic dopaminergic circuits (Solinas et al, 2008 ; Chauvet et al, 2011 ; Galaj et al, 2016 ), even when EE is introduced during adulthood (Del Arco et al, 2007 ; Segovia et al, 2010 ), and there is ample evidence indicating a primary anxiolytic role for EE (Benaroya-Milshtein et al, 2004 ; Peña et al, 2006 , 2009 ; Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ; Bahi, 2017b ). With the present results, we cannot conclude the precise neurobehavioral mechanisms underlying the observed therapeutic and protective impact of EE on binge-like EtOH intake; however, we discuss next EtOH consumption data associated with EE vs.…”

Section: Discussionmentioning

confidence: 99%

“…Growing experimental evidence highlights the additional ability of EE exposure during adulthood as a therapeutic tool for modulating drug intake, drug reward and drug-relapse in animals with a previous history of continued drug consumption. Thus, exposure to EE during adulthood significantly reduced responses in cue-induced reinstatement of heroin seeking after continued heroin self-administration in a fixed ratio schedule in Long Evans rats (Galaj et al, 2016 ). EE also reduced methamphetamine-induced behavioral deficits and the risk of drug-withdrawal triggered by drug-relapse in Wistar rats (Hajheidari et al, 2015 ) and methamphetamine-, heroin- and nicotine- seeking behaviors as well, as assessed in a fixed schedule ratio in Sprague-Dawley rats (Sikora et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Environmental Enrichment During Adolescence Acts as a Protective and Therapeutic Tool for Ethanol Binge-Drinking, Anxiety-Like, Novelty Seeking and Compulsive-Like Behaviors in C57BL/6J Mice During Adulthood

Rodríguez-Ortega

Fuente

Amo

et al. 2018

Front. Behav. Neurosci.

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Repetitive drug/ethanol (EtOH) binge-like consumption during pre-addictive stages favors a transition to addiction in vulnerable organisms. Experimental evidence points to the therapeutic and preventive effects of environmental enrichment (EE) on drug and EtOH addiction; however, little is known regarding EE modulation of binge-like consumption in non-dependent organisms. Here, we explore the impact of early EE on binge-like EtOH consumption: (1) we test whether early EE exposure prevents binge-like EtOH intake (20% v/v) in adult mice under an intermittent drinking in the dark (iDID) schedule; (2) we evaluate the therapeutic effects of EE housing conditions on binge-like EtOH consumption in adult animals; and (3) we compare novelty-seeking and compulsive-like behaviors, and anxiety-like behavior, as measured by the Hole Board (HB) and Elevated Plus Maze (EPM) tests, respectively, in adult EE/standard environment (SE) animals. Adolescent (postnatal day 28; PND28) mice were randomly allocated to two housing conditions (4 animals/cage): EE or SE. At PND67 all the animals were exposed to a schedule of EtOH binge-like iDID. On PND92 half of the animals in each environmental condition (EE and SE) were randomly allocated to two subgroups in a crossover design, where environmental conditions were kept similar to those previously experienced or switched, finally leading to four experimental conditions: EE-EE, EE-SE, SE-SE, and SE-EE. EtOH binge-like consumption continued until PND140, when EPM and HB tests were finally conducted. The main observations were: (1) EE-reared mice showed lower EtOH binge-like intake than SE-reared mice during adulthood, which supports a protective role for EE. (2) when adult EtOH drinking SE-reared mice were switched to EE conditions, a reduction in EtOH binge-like consumption was observed, suggesting a therapeutic role for EE; however, losing EE during adulthood triggered a progressive increase in EtOH binge-like intake. Moreover, (3) EE-housed adult animals with long-term exposure to EtOH binge-drinking showed lower anxiety-like, compulsive-like, and novelty-seeking behaviors than SE-housed mice, irrespective of the specific housing conditions during adolescence. We discuss the primary impact of EE on anxiety-like neurobehavioral brain systems through which it secondarily modulates EtOH binge-like drinking.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Environmental Enrichment During Adolescence Acts as a Protective and Therapeutic Tool for Ethanol Binge-Drinking, Anxiety-Like, Novelty Seeking and Compulsive-Like Behaviors in C57BL/6J Mice During Adulthood

Rodríguez-Ortega

Fuente

Amo

et al. 2018

Front. Behav. Neurosci.

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“…Lower levels of impulsive choice are also associated with decreased susceptibility to drug abuse [13, 62, 64], and enrichment has been reported to reduce impulsive choice [16, 17]. Exposure to novelty enrichment following heroin self-administration has been shown to reduce the enriched rats’ cue-induced reinstatement of drug-seeking behavior [65]. Given that novelty enrichment alone increased impulsive choice behavior (i.e., lower self-control), this suggests the possibility of distinct mechanisms of choice behavior and those involved in drug-taking.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of social and novelty enrichment on individual differences in impulsivity and behavioral flexibility

Wang

Marshall

Kirkpatrick

2017

Behavioural Brain Research

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Early life experience profoundly impacts behavior and cognitive functions in rats. The present study investigated how the presence of conspecifics and/or novel objects, could independently influence individual differences in impulsivity and behavioral flexibility. Twenty-four rats were reared in an isolated condition, an isolated condition with a novel object, a pair-housed social condition, or a pair-housed social condition with a novel object. The rats were then tested on an impulsive choice task, a behavioral flexibility task, and an impulsive action task. Novelty enrichment produced an overall increase in impulsive choice, while social enrichment decreased impulsive choice in the absence of novelty enrichment and also produced an overall increase in impulsive action. In the behavioral flexibility task, social enrichment increased regressive errors, whereas both social and novelty enrichment reduced never reinforced errors. Individual differences analyses indicated a significant relationship between performance in the behavioral flexibility and impulsive action tasks, which may reflect a common psychological correlate of action inhibition. Moreover, there was a relationship between delay sensitivity in the impulsive choice task and performance on the DRL and behavioral flexibility tasks, suggesting a dual role for timing and inhibitory processes in driving the interrelationship between these tasks. Overall, these results indicate that social and novelty enrichment produce distinct effects on impulsivity and adaptability, suggesting the need to parse out the different elements of enrichment in future studies. Further research is warranted to better understand how individual differences in sensitivity to enrichment affect individuals’ interactions with and the resulting consequences of the rearing environment.

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“…On the other hand, there is consistent scientific evidence supporting the therapeutic effect of EE access during adulthood to modulate drug consumption, drug reward and drug relapse. Thus, in Long Evans rats trained for continued heroin administration in a FR program, EE access blunted operant responses in cue-induced reinstatement of heroin seeking (Galaj et al, 2016 ). In Wistar rats, exposure to EE decreased behavioral deficits induced by methamphetamine and the risk of withdrawal unleashed by relapse (Hajheidari et al, 2015 ).…”

Section: Environmental Enrichment Exposure Regulates Drug and Sugar Imentioning

confidence: 99%

Environmental Enrichment Modulates Drug Addiction and Binge-Like Consumption of Highly Rewarding Substances: A Role for Anxiety and Compulsivity Brain Systems?

Rodríguez-Ortega

Cubero

2018

Front. Behav. Neurosci.

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Drug addiction is a chronic disorder comprising components of both impulsivity and compulsivity in the so called “addiction cycle” which develops over time from early non-dependent, repetitive, binge-consumption to later post-dependent compulsive consumption. Thus, frequent binge-like intake is a typical pattern of excessive drug intake characteristic of the pre-dependent phase of the addiction cycle, which represent an important risk factor to develop addiction in vulnerable individuals. In this framework, it is of paramount interest to further understand the earliest stage of the addiction cycle so novel approaches would emerge aimed to control repetitive episodes of binge-consumption in non-dependent subjects, protecting vulnerable individuals from transition to dependence. Environmental enrichment (EE) is a preclinical animal model in which animals are housed under novel, social enriched conditions, which allows exercising and provides sensory and cognitive stimulation. EE promotes important improvements for a variety of cognitive processes and clear therapeutic and protective effects preventing ethanol (EtOH) and drug addiction as well. Interestingly, recent observations suggest that EE might additionally modulate binge-like intake of highly palatable caloric substances, including EtOH, which suggests the ability of EE to regulate consumption during the initial stage of the addiction cycle. We have proposed that EE protective and therapeutic effects on binge-consumption of palatable substances might primarily be mediated by the modulatory control that EE exerts on anxiety and impulsivity/compulsivity traits, which are all risk factors favoring transition to drug addiction.

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Environmental enrichment as a potential intervention for heroin seeking

Cited by 30 publications

References 71 publications

Environmental Enrichment During Adolescence Acts as a Protective and Therapeutic Tool for Ethanol Binge-Drinking, Anxiety-Like, Novelty Seeking and Compulsive-Like Behaviors in C57BL/6J Mice During Adulthood

Environmental Enrichment During Adolescence Acts as a Protective and Therapeutic Tool for Ethanol Binge-Drinking, Anxiety-Like, Novelty Seeking and Compulsive-Like Behaviors in C57BL/6J Mice During Adulthood

Differential effects of social and novelty enrichment on individual differences in impulsivity and behavioral flexibility

Environmental Enrichment Modulates Drug Addiction and Binge-Like Consumption of Highly Rewarding Substances: A Role for Anxiety and Compulsivity Brain Systems?

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