Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake

Abstract

Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake.

Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons

“…Injectors were left in place for an additional minute before being removed. Animals were placed on the EZM illuminated by a 7.5 W incandescent bulb 5 min after the microinjection (Nobre, 2016). An ace monochrome camera (Basler) along with EthoVision XT Video-Tracking Software (Noldus) were used to track center point, tail base, and nose point throughout the 5 min test to assess anxiety-like behavior and general locomotion.…”

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

“…Interestingly, a number of studies have found that EE exposure reduces anxiety-like responses, compulsive repetitive behaviors and novelty-seeking behaviors, which might represent a potential neurobehavioral mechanism by which EE has a modulatory role on continued drug/EtOH intake. Thus, EE exposure triggered anxiolytic-like responses as measured by the Elevated Plus Maze (EPM) in mice and rats (Peña et al, 2006 , 2009 ; Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ; Bahi, 2017b ), the Light/dark-box test in mice (Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ), and the Elevated Zero Maze (EZM) test in rats (Nobre, 2016 ). Furthermore, in SHR rats, EE exposure reduced high exploration of a novel environment in an open field (OF) test indicating a reduction in EE-elicited response to novelty (de Carvalho et al, 2010 ) and significantly attenuated the development of repetitive motor behaviors (Muehlmann et al, 2012 ; Bechard and Lewis, 2016 ; Bechard et al, 2016 ), a sign of compulsivity-like behavior in drug addiction and other disorders (Figee et al, 2016 ).…”

“…Given the aforementioned behavioral evidence that EE exposure exerts a modulatory impact on compulsive-like behavior (Muehlmann et al, 2012 ; Bechard and Lewis, 2016 ), anxiety-like responses (Peña et al, 2006 , 2009 ; Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ; Nobre, 2016 ; Bahi, 2017b ), and novelty-seeking behavior (de Carvalho et al, 2010 ), all of which are risk factors to develop EtOH and drug addiction, the third objective in this study addressed whether animals on enriched housing conditions and exposed to continued EtOH binge-like intake show reduced novelty-seeking and compulsive-like behaviors, and anxiety-like behavior, as measured by the Hole Board (HB) and EPM tests, respectively, compared with animals in standard housing conditions.…”

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

“…Importantly, there is consistent scientific evidence pointing to the EE ability to regulate anxiety- and compulsivity-like behaviors as well as novelty-seeking traits. Thus, exposure to EE housing conditions reduced anxiety-like behaviors as measured by the Elevated Plus Maze (EPM) in both rats and mice (Peña et al, 2006 , 2009 ; Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ; Bahi, 2017b ), the Zero Maze (EZM) in rats (Nobre, 2016 ) and the light/dark box in mice (Sztainberg et al, 2010 ; Ragu Varman and Rajan, 2015 ). Moreover, EE housing conditions decreased motor exploration in SHR rats in an open field test (de Carvalho et al, 2010 ) and did blunt the onset of repetitive compulsive motor responses (Muehlmann et al, 2012 ; Bechard and Lewis, 2016 ; Bechard et al, 2016 ), which has been considered a manifestation of compulsivity in drug addiction (Figee et al, 2016 ).…”