Adolescent female rats are more resistant than males to the effects of early stress on prefrontal cortex and impulsive behavior

Spivey, Jaclyn M.; Shumake, Jason; Colorado, René A.; Conejo, Nélida M.; González-Pardo, Héctor; González-Lima, Francisco

doi:10.1002/dev.20362

Cited by 41 publications

(37 citation statements)

References 59 publications

(101 reference statements)

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“…All females, regardless of maternal opioid history showed increased locomotor activity compared with males in response to a novel environment. This has been shown repeatedly and recapitulates what is known in the literature (Hensleigh et al, 2011; Spivey et al, 2009; Wooters et al, 2006). CPP is posited to measure cue-elicited conditioning that can motivate drug-taking behavior (Bardo et al, 1995; Robbins and Ehrman, 1992).…”

Section: Discussionsupporting

confidence: 84%

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring

2016

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Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30–39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA.

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Section: Discussionsupporting

confidence: 84%

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring

2016

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“…For instance, corticotrophin-releasing hormone and glucocorticoid receptor mRNA levels are reduced in the prefrontal cortex of maternally separated rats (Ladd et al, 2005). Reductions in prefrontal cortical thickness (Spivey et al, 2009) and in dendritic processes of the prefrontal pyramidal neurons have also been demonstrated in maternally separated rats (Monroy et al, 2010; Pascual & Zamora-Leon, 2007). In addition, irregular patterns of interneuron development in the medial prefrontal cortex of maternally separated animals have been found in another rodent species (Helmeke et al, 2008).…”

Section: Discussionmentioning

confidence: 97%

Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain

Spivey

Padilla

Shumake³

et al. 2011

Brain Research

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This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life.

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“…The vertical (dorsoventral) distance was measured parallel to the midsagittal line, using the rhinal fissure endpoint to center the placement of the line. The horizontal (mediolateral) distance was measured perpendicular to the midsagittal line, crossing midway through the dorsoventral line80.…”

Section: Methodsmentioning

confidence: 99%

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

McCreary

Erickson

Hao

et al. 2016

Sci Rep

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Ancestral stress can program stress sensitivity and health trajectories across multiple generations. While ancestral stress is uncontrollable to the filial generations, it is critical to identify therapies that overcome transgenerational programming. Here we report that prenatal stress in rats generates a transgenerationally heritable endocrine and epigenetic footprint and elevated stress sensitivity which can be alleviated by beneficial experiences in later life. Ancestral stress led to downregulated glucocorticoid receptor and prefrontal cortex neuronal densities along with precocious development of anxiety-like behaviours. Environmental enrichment (EE) during adolescence mitigated endocrine and neuronal markers of stress and improved miR-182 expression linked to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) regulation in stressed lineages. Thus, EE may serve as a powerful intervention for adverse transgenerational programming through microRNA-mediated regulation of BDNF and NT-3 pathways. The identification of microRNAs that mediate the actions of EE highlights new therapeutic strategies for mental health conditions and psychiatric disease.

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Adolescent female rats are more resistant than males to the effects of early stress on prefrontal cortex and impulsive behavior

Cited by 41 publications

References 59 publications

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring

Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring

Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

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