RESUMO
Despite the presence of multiple pharmacotherapeutic options, incidence rates for depressive disorders continue to rise. Nonpharmacological approaches (e.g., cognitive and behavioral therapies) exhibit encouraging efficacy rates; however, a lack of preclinical models has prevented progress in the identification of relevant neurobiological mechanisms of these approaches. Accordingly, the effort-based reward (EBR) preclinical model exposes rats to response-outcome (R-O) contingencies and provides an opportunity to investigate behavioral clinical approaches. In the current study, male and female rats were assigned to either an EBR contingent- or noncontingent-trained group and exposed to 7 weeks of training. Neuroadaptive cognitive responses were assessed in a cognitive uncertainty task (UT) and an object pattern separation task (OPST). Although no significant effects of EBR were observed in the UT, EBR contingent-trained rats approached the novel panel in the most difficult trial of the OPST faster than the noncontingent-trained group. Additionally, female EBR contingent-trained rats exhibited increased engagement with the novel stimulus panel across all trials. Examination of brain-derived neurotrophic factor (BDNF) in the lateral habenula (LHb), a putative neurobiological target for depressive symptoms, revealed lower BDNF immunoreactivity in EBR contingent-trained rats. Females in both training groups exhibited higher dehydroepiandrosterone/cortisol (DHEA/CORT) ratios, suggesting, along with the increased engagement with novel stimulus panels, that female rats may be more responsive to EBR contingency training than males. Together, these results suggest that EBR contingency training offers promise as a preclinical rat model for behavioral therapeutic interventions for depressive symptoms leading to a clearer understanding of putative neurobiological mechanisms.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Animais , Cognição , Depressão/psicologia , Depressão/terapia , Feminino , Masculino , Ratos , Ratos Long-Evans , RecompensaRESUMO
When a maternal rat nurtures her pups, she relies on adequate resources to provide optimal care for her offspring. Accordingly, limited environmental resources may result in atypical maternal care, disrupting various developmental outcomes. In the current study, maternal Long-Evans rats were randomly assigned to either a standard resource (SR) group, provided with four cups of bedding and two paper towels for nesting material or a limited resource (LR) group, provided with a quarter of the bedding and nesting material provided for the SR group. Offspring were monitored at various developmental phases throughout the study. After weaning, pups were housed in same-sex dyads in environments with SRs for continued observations. Subsequent behavioral tests revealed a sex × resource interaction in play behavior on PND 28; specifically, LR reduced play attacks in males while LR increased play attacks in females. A sex × resource interaction was also observed in anxiety-related responses in the open field task with an increase in thigmotaxis in LR females and, in the social interaction task, females exhibited more external rears oriented away from the social target. Focusing on morphological variables, tail length measurements of LR males and females were shorter on PND 9, 16, and 21; however, differences in tail length were no longer present at PND 35. Following the behavioral assessments, animals were perfused at 56 days of age and subsequent immunohistochemical assays indicated increased glucocorticoid receptors in the lateral habenula of LR offspring and higher c-Fos immunoreactivity in the basolateral amygdala of SR offspring. Further, when tail vertebrae and tail tendons were assessed via micro-CT and hydroxyproline assays, results indicated increased trabecular separation, decreased bone volume fraction, and decreased connectivity density in bones, along with reduced collagen concentration in tendons in the LR animals. In sum, although the restricted resources only persisted for a brief duration, the effects appear to be far-reaching and pervasive in this early life stress animal model.
RESUMO
Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.