Elsevier

Behavioural Brain Research

Volume 208, Issue 1, 17 March 2010, Pages 231-236
Behavioural Brain Research

Research report
Environmental enrichment reduces the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats

https://doi.org/10.1016/j.bbr.2009.11.043Get rights and content

Abstract

The present study investigated the consequences of environmental enrichment on the impact of novelty and motivational properties of ethanol in spontaneously hypertensive rats (SHR), a validated model of attention deficit hyperactivity disorder (ADHD). This rat strain displays increased sensitivity to distinct classes of abused drugs, which makes it an interesting model for the study of the association between ADHD and drug abuse. Female SHR reared from weaning to adulthood in standard (SE) or enriched (EE) environment were tested on novelty-induced locomotion, saccharin consumption, ethanol consumption (forced and free-choice schedules) and ethanol-induced conditioned place preference (CPP). SHR reared in an EE showed reduced novelty-induced locomotion, consumed less saccharin and ethanol in a forced schedule and showed less ethanol preference in a free-choice schedule compared to SE rats. Moreover, EE rats did not develop CPP, whereas SE rats developed preference for ethanol (1.2 g/kg). These results show that exposure to stimuli mimicking positive life experiences (environmental enrichment) induces persistent changes in the reward/motivational system of female SHR, suggesting an important role of the familiar environment during early stages of the neurodevelopment on the co-morbidity of ADHD and drug abuse.

Introduction

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder that develops from a complex gene–environment interaction [5], [9], [38]. It is characterized by the presence of three primary symptoms: hyperactivity, inattention, and impulsivity [15]. ADHD is one of the most common childhood psychiatric disorders [8] affecting between 5 and 10% of primary-school children in the U.S.A. ADHD symptoms often persist until adolescence and adulthood in nearly 50% of the children affected by disorder [4], [43]. The behavioral profile of ADHD children has been suggested to be secondary to a dysfunction of reinforcement mechanisms, which associated with poor judgment and/or impulsive behavior in social settings seems to predispose the ADHD adolescent to the earlier onset of drug consumption and abuse [17], [32].

Indeed, several studies have shown that ADHD represents a high risk factor for drug addiction and the co-occurrence between ADHD and substance abuse has been observed in about 40–70% of patients [10], [16], [37], [42], [43]. Although frequently observed, the co-morbidity between ADHD and substance abuse remains poorly understood.

The spontaneously hypertensive rat (SHR) strain has been considered a validated animal model of ADHD, displaying good face, construct, and predictive validity [29], [30], [31]. Moreover, it has been proposed that this rat strain constitutes an interesting model for the study of the association between ADHD and drug abuse, since in addition to showing ADHD-like behavioral symptomatology SHR display increased sensitivity to distinct classes of abused drugs, such as cocaine, cannabinoids, ethanol and others (for a recent review, see [41]).

Additionally, SHR (particularly females) express higher preference for ethanol and increased ethanol consumption than other rat strains [6], [40]. The sensitivity to the reinforcing effects of drugs might confer increased tendency to the development of addiction, being one of the first steps of individual vulnerability [11]. Exposure to negative environmental influences during development increases the reinforcing effects of drugs and predisposes to substance abuse [19], [20], [33]. On the other hand, positive life experiences might confer resistance to the reinforcing effects of drugs, as studied by means of environmental enrichment (EE) protocols (for a recent review, see [36]). In view of this risk, although psychopharmacology has been considered the primary therapeutic approach to ADHD, the search for alternative/complementary non-pharmacological therapeutic strategies for ADHD associated with substance abuse is a field of great interest. Environmental enrichment stands out as the most used strategy for cognitive stimulation and overall improvement in CNS maturation during development. In short, the term refers to a strategy employing a stimulating social environment, full of novelty and encouragements to perform physical activity and to interact with social partners [28], [39]. Our hypothesis was that an animal model of ADHD reared in a playful and stimulating enriched environment would show relatively reduced sensitivity to external reinforcers, such as novelty and drugs of abuse. Hence, the objective of the present study was to investigate the consequences of environmental enrichment during neurodevelopment – from early stages of life to adulthood – on the impact of novelty and rewarding properties of ethanol on SHR. Animals reared in the standard or enriched environment were tested during adulthood on novelty-induced locomotion, saccharin consumption, ethanol consumption (forced and free-choice schedules) and on ethanol-induced conditioned place preference (CPP).

Section snippets

Subjects

One hundred and four female SHR from our own colony were used in the experimental procedures. Our colony is derived from the original cohort of animals obtained from the Behavioral Genetics Laboratory from UFSC (Florianópolis, SC, Brazil) [26] and maintained under a brother–sister breeding system in our laboratory. The animals were reared in standard or enriched-housing conditions from weaning (post-natal day 21) to adulthood (approximately 3 months of age). They were maintained in a room under

Open Field

Student's t test indicated a significant difference between the two housing environments in total locomotion [t = 5.39, p < 0.0001; Fig. 1A] and total number of rearings [t = 4.69, p < 0.001; Fig. 1B] in the OF test. The analysis showed that animals reared in enriched-housing conditions presented reduced exploration of a new environment.

Activity cage

Two-way ANOVA with repeated-measures analysis for locomotor activity, measured for 60 min in the activity cage (10-min bins), indicated a significant effect of

Discussion

One interesting point of the present study is that the widely reported beneficial/protective effects of the EE on vulnerability to drug abuse can be extended to EtOH. The general conclusion from the self-administration experiments is that EE animals consume less EtOH than animals reared in SE, either on a forced or free-choice schedule. Apparently, EE animals also do not prefer to drink EtOH as compared to regular tap water, as opposed to SE animals, and they showed reduced consumption of novel

Acknowledgements

This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Programa de Apoio aos Núcleos de Excelência (PRONEX), and the Fundação de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC), all of Brazil. CRC, FAP and PP received a scholarship from the CNPq. RNT is the holder of a CNPq fellowship.

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