Environmental enrichment can modulate mild and chronic stress, responses to anxiogenic stimuli as well as drug vulnerability in a number of animal models. The current study was designed to examine the impact of postnatal environmental enrichment on selectively bred 4th generation high (HAn) and low anxiety (LAn) male rats. After weaning, animals were placed in isolated, social and enriched environments (e.g., toys, wheels, ropes, changed weekly). We measured anxiety-like behavior (ALB) on the elevated plus maze (EPM; trial 1 at PND 46, trial 2 at PND 63), amphetamine (0.5 mg/kg, IP)-induced locomotor behavior, basal and post anxiogenic stimuli changes in (1) plasma corticosterone, (2) blood pressure and (3) core body temperature. Initially, animals showed consistent trait differences on EPM with HAn showing more ALB but after 40 days in select housing, HAn rats reared in an enriched environment (EE) showed less ALB and diminished AMPH-induced activity compared to HAn animals housed in isolated (IE) and social environments (SE). In the physiological tests, animals housed in EE showed elevated adrenocortical responses to forced novel object exposure but decreased body temperature and blood pressure changes after an air puff stressor. All animals reared in EE and SE had elevated BDNF-positive cells in the central amygdala (CeA), CA1 and CA2 hippocampal regions and the caudate putamen, but these differences were most pronounced in HAn rats for CeA, CA1 and CA2. Overall, these findings suggest that environmental enrichment offers benefits for trait anxiety rats including a reduction in behavioral and physiological responses to anxiogenic stimuli and amphetamine sensitivity, and these responses correlate with changes in BDNF expression in the central amygdala, hippocampus and the caudate putamen.

Environmental enrichment attenuates the response to psychostimulants and has been shown to reduce both anxiety and stress-related behaviors. Since stress is a major vulnerability factor for addiction, we investigated whether enrichment could reverse stress profiles in high anxious rats as well as reduce their amphetamine sensitivity. Using selectively-bred high and low anxiety males (filial 3) from enriched, social or isolated environments, we tested elevated plus maze exploration, novelty place preference and amphetamine (AMPH; 0.5 mg/kg, IP)-induced hyperactivity. We measured plasma corticosterone (CORT) response after forced novel object exposure, phosphorylation of the tropomyosin-related kinase B receptor (pTrkB) in the hippocampus and striatum, and dopamine (D2) receptor mRNA levels in the striatum and nucleus accumbens. Results indicate that high anxiety animals reared in social or enriched environments spent more time on open arms of the EPM while low anxiety animals raised in enriched environments spent more time on open arms when compared to either isolated or social groups. There were no group differences or interactions found for novelty place preference. Enriched environments decreased the response to AMPH and stress-induced CORT regardless of trait but selectively decreased pTrkB and increased D2 mRNA levels in high anxiety animals. The results suggest that selectively-bred trait anxiety rats show state anxiety that is influenced by rearing environments, and D2 protein levels and BDNF/TrkB signaling may differentially contribute to integrating these effects.

In clinical populations, prevalence rates for a number of anxiety disorders differ between males and females and gonadal hormones are thought to contribute to these differences. While these hormones have been shown to modulate the anxiolytic effects of the benzodiazepine agonist diazepam in some models, findings are inconsistent. Here, we tested for sex differences in response to anxiogenic stimuli following a 30-min diazepam (1.0 mg/kg) pre-treatment in male and female rats showing high (HAn) and low (LAn) anxiety-like behavior on the elevated plus maze. Acute diazepam administration resulted in decreased anxiety-like behavior only in HAn males as demonstrated by a significant increase in percent open arm time in the elevated plus maze (EPM). Immunohistochemical analysis for parvalbumin (PV; a calcium-binding protein that selectively stains GABAergic neurons) in central amygdala (CeA), caudate putamen (CPu) and the hippocampus indicated the number of GABAergic interneurons in these areas differed across sex and anxiety trait. In the CPu, females had significantly more PV-immunoreactive (IR) cells than males, and LAn females had greater PV-IR neurons than HAn females. In the CeA, males displayed an increased number of PV-IR neurons compared to females, with no differences found between LAn and HAn. Further, trait differences were evident in the CA2 region of the hippocampus, regardless of sex. Taken together, these data suggest that gonadal hormones and trait anxiety may influence the sensitivity to the anti-anxiety effects of diazepam and these differences may be due in part to the distribution of GABA-containing interneurons.

Increasing the use of evidence-based programs (EBPs) in community settings is critical for improving health and reducing disparities. Community-based organizations (CBOs) and faith-based organizations (FBOs) have tremendous reach and trust within underserved communities, but their impact is constrained by limited staff capacity to use EBPs. This exploratory study sought to identify design and delivery considerations that could increase the impact of capacity-building interventions for CBOs and FBOs working with underserved communities. Data come from a community-based participatory research project addressing cancer disparities in Black, Latino, and Brazilian communities from Greater Boston and Greater Lawrence, Massachusetts. We conducted four focus group discussions with program coordinators in CBOs and FBOs (n = 27) and key informant interviews with CBO and FBO leaders (n = 15). Three researchers analyzed the data using a multi-stage coding process that included both prefigured and emergent codes. Key design considerations included embedding customized capacity-building interventions into community networks with local experts, supporting ongoing engagement with the intervention via a range of resources and communication channels, and addressing resource constraints. Regarding the contextual factors that should influence capacity-building intervention content, participants highlighted resource constraints, environments in which EBP use is not the norm, and challenges linking available programs with the multi-level barriers to good health faced by community members. Overall, the study highlights the need for integrated, long-term capacity-building efforts developed in partnership with, and ultimately sustained by, local organizations.

Maternal care has been shown to affect the development of behavioral and endocrine systems. In rats, periodic maternal deprivation (PMD) serves as an early life stressor that directly influences maternal care by promoting more pup-directed behaviors in stressed dams. To further assess the qualities of PMD that may ameliorate long-term anxiety effects in trait anxiety animals, we coded behaviors across lactation (postnatal day (PND) 5, 16, 21) in dams phenotyped as high (HAn) and low-anxiety (LAn). We assessed anxiety-like behavior in male offspring using the elevated plus maze (EPM), focusing on percent open arm (%OA) time and latency to enter OA (OA LAT) as a measure of anxiety-like behavior. Finally, we examined the brains of representative male pups to determine if the stress-related protein brain-derived neurotrophic factor (BDNF) might show persistent changes in the amygdala. Dams phenotyped as HAn had lower %OA time and longer OA LAT relative to dams designated as LAn. During PMD, HAn dams had higher incidences of lick-grooming (L/G) and more pup-directed behaviors on PND 5 and 16 compared to LAn dams. Further, as adults, HAn male offspring exhibited less anxiety traits than their maternal line with greater %OA time and %OA entries relative to LAn. HAn offspring showed markedly more BDNF immunoreacted cells in the amygdala than LAn. The combination of these findings suggests that the mild stressor, PMD alters anxiety-like behavior in offspring likely by influencing HAn dams’ L/G activity and altering stress related proteins in the amygdala.