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Strain and sex dependent effects of isolation housing relative to environmental enrichment on operant sensation seeking in mice.

ABSTRACT: Sensation seeking is a multidimensional phenotype that predicts the development of drug addiction in humans and addiction-like drug seeking in rodents. Several lines of evidence suggest that chronic stress increases sensation seeking and addiction-like drug seeking through common genetic mechanisms. Discovery and characterization of these mechanisms would reveal how chronic stress interacts with the genome to influence sensation seeking and how drugs of abuse hijack these fundamental reward mechanisms to drive addiction. To this end, we tested the hypothesis that chronic isolation housing stress (relative to environmental enrichment) influences operant sensation seeking as a function of strain, sex, or their interaction. To determine if the BXD recombinant inbred panel could be used to identify genetic and epigenetic mechanisms underlying any identified gene-by-environment interactions, we used mice from the two BXD founder strains. Following 10 weeks of differential housing, we assessed operant sensation seeking using several reinforcement schedules. The primary finding from this study was that DBA/2J but not C57BL/6J mice were significantly vulnerable to an isolation-induced increase (relative to environmental enrichment) in sensation seeking during extinction when the sensory reward was no longer available; this effect was significantly more robust in females. These data reveal a previously unknown isolation-induced effect on extinction of operant sensation seeking that is sex-dependent, addiction-relevant, and that can be dissected using the BXD recombinant inbred panel.

SUBMITTER: Dickson PE

PROVIDER: S-EPMC8426458 | biostudies-literature |

REPOSITORIES: biostudies-literature

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microRNA regulation related to the protective effects of environmental enrichment against cocaine-seeking behavior

Project description:MicroRNAs are “master regulators” of gene expression. To investigate microRNAs involved in the incentive motivation for cocaine elicited by exposure to cocaine-associated cues, we conducted NanoString nCounter analyses of microRNA expression in the nucleus accumbens shell of male rats that had been tested for cue reactivity in a previous study. These rats had been trained to self-administer cocaine while living in isolate housing, then during a subsequent 21-day forced abstinence period they either stayed under isolate housing or switched to environmental enrichment (EE), as this EE intervention is known to decrease cocaine seeking. This allowed us to create groups of “high” and “low” cocaine seekers using a median split of cocaine-seeking behavior. We conducted a differential expression analysis across these two groups that identified 33 miRNAs that were differentially altered in the nucleus accumbens shell. Predicted mRNA targets of these microRNAs are implicated in synaptic plasticity and neuronal signaling. Some of these microRNAs have previously been implicated in substance use disorders, while others are predicted to target large numbers of cocaine-related genes. Of the 33 differentially expressed microRNAs, 8 were specifically downregulated in the low-seeking group and another set of 8 had expression levels that were significantly correlated with cocaine-seeking. These findings suggest that processes involved in cocaine-seeking behavior may alter, or be altered by, multiple microRNAs. Further research examining the mechanisms involved in these microRNA changes and their effects on signaling may reveal novel therapeutic targets for attenuating drug craving.

2020-12-25 | GSE153524 | GEO

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Project description:Despite extensive evidence from cohort studies linking exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) to numerous cognitive outcomes in children and adolescents, very few studies addressed reward sensitivity, a key dimension of emotional regulation. The present study aimed to examine associations between pre- and postnatal exposure to these environmental neurotoxicants and sensation seeking, a behavioral feature of reward. A total of 207 Inuit adolescents (mean age = 18.5, SD = 1.2) from Nunavik, Canada, completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking- 2 (SS-2), two self-report questionnaires assessing proneness to sensation seeking. Prenatal, childhood and adolescent exposure to Pb, Hg and PCBs were measured in cord blood at birth and blood samples at 11 years of age and at time of testing. Multiple linear regression models were performed, potential confounders including participants' sociodemographic characteristics and nutrient fish intake were considered. Results showed that higher child blood levels of Pb (b = -0.18, p = 0.01) and PCB-153 (b = -0.16, p = 0.06) were associated with lower BSSS-4 total scores, while cord and adolescent blood PCB-153 levels were significantly related to lower SS2 total scores (b = -0.15, p = 0.04; b = -0.24, p = 0.004). Such associations persisted after further adjustment for co-exposure to concurrent contaminants. These associations were influenced by self-report positive affect and marginally moderated by sex. Sex differences were only observed for child PCB exposure, with the association for risk-taking sensation seeking observed only in girls but not in boys. Further research is warranted to assess the extent to which reduced sensation seeking in chronically exposed individuals affects their behaviors, well-being, and emotional regulation.

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Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data.

Project description:Animal welfare requires the adequate housing of animals to ensure health and well-being. The application of environmental enrichment is a way to improve the well-being of laboratory animals. However, it is important to know whether these enrichment items can be incorporated in experimental mouse husbandry without creating a divide between past and future experimental results. Previous small-scale studies have been inconsistent throughout the literature, and it is not yet completely understood whether and how enrichment might endanger comparability of results of scientific experiments. Here, we measured the effect on means and variability of 164 physiological parameters in 3 conditions: with nesting material with or without a shelter, comparing these 2 conditions to a "barren" regime without any enrichments. We studied a total of 360 mice from each of 2 mouse strains (C57BL/6NTac and DBA/2NCrl) and both sexes for each of the 3 conditions. Our study indicates that enrichment affects the mean values of some of the 164 parameters with no consistent effects on variability. However, the influence of enrichment appears negligible compared to the effects of other influencing factors. Therefore, nesting material and shelters may be used to improve animal welfare without impairment of experimental outcome or loss of comparability to previous data collected under barren housing conditions.

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