Search

The rodent medial prefrontal cortex (mPFC) is anatomically divided into cingulate (Cg1), prelimbic (PrL), and infralimbic (IL) subareas. The left and right mPFC (L and RmPFC) process emotional responses induced by stress-related stimuli, and LmPFC and RmPFC inhibition elicit anxiogenesis and anxiolysis, respectively. Here we sought to investigate (i) the mPFC functional laterality on social avoidance/anxiogenic-like behaviors in male mice subjected to chronic social defeat stress (SDS), (ii) the effects of left prelimbic (PrL) inhibition (with local injection of CoCl2) on the RmPFC glutamatergic neuronal activation pattern (immunofluorescence assay), and (iii) the effects of the dorsal right mPFC (Cg1 + PrL) NMDA receptor blockade (with local injection of AP7) on the anxiety induced by left dorsal mPFC inhibition in mice exposed to the elevated plus maze (EPM). Results showed that chronic SDS induced anxiogenic-like behaviors followed by the rise of ΔFosB labeling and by ΔFosB + CaMKII double-labeling bilaterally in the Cg1 and IL subareas of the mPFC. Chronic SDS also increased ΔFosB and by ΔFosB + CaMKII labeling only on the right PrL. Also, the left PrL inhibition increased cFos + CaMKII labeling in the contralateral PrL and IL. Moreover, anxiogenesis induced by the left PrL inhibition was blocked by NMDA receptor antagonist AP7 injected into the right PrL. These findings suggest the lateralized control of the glutamatergic neurotransmission in the modulation of emotional-like responses in mice subjected to chronic SDS.

The rodent medial prefrontal cortex (mPFC) is anatomically divided into cingulate (Cg1), prelimbic (PrL), and infralimbic (IL) subareas. The left and right mPFC (L and RmPFC) process emotional responses induced by stress-related stimuli, and LmPFC and RmPFC inhibition elicit anxiogenesis and anxiolysis, respectively. Here we sought to investigate (i) the mPFC functional laterality on social avoidance/anxiogenic-like behaviors in male mice subjected to chronic social defeat stress (SDS), (ii) the effects of left prelimbic (PrL) inhibition (with local injection of CoCl2) on the RmPFC glutamatergic neuronal activation pattern (immunofluorescence assay), and (iii) the effects of the dorsal right mPFC (Cg1 + PrL) NMDA receptor blockade (with local injection of AP7) on the anxiety induced by left dorsal mPFC inhibition in mice exposed to the elevated plus maze (EPM). Results showed that chronic SDS induced anxiogenic-like behaviors followed by the rise of ΔFosB labeling and by ΔFosB + CaMKII double-labeling bilaterally in the Cg1 and IL subareas of the mPFC. Chronic SDS also increased ΔFosB and by ΔFosB + CaMKII labeling only on the right PrL. Also, the left PrL inhibition increased cFos + CaMKII labeling in the contralateral PrL and IL. Moreover, anxiogenesis induced by the left PrL inhibition was blocked by NMDA receptor antagonist AP7 injected into the right PrL. These findings suggest the lateralized control of the glutamatergic neurotransmission in the modulation of emotional-like responses in mice subjected to chronic SDS. [ABSTRACT FROM AUTHOR]

While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. [ABSTRACT FROM AUTHOR]

Regulation of body weight is an important strategy for small prey animals to avoid capture. Field and laboratory studies have shown that prey animals reduce body size when subjected to long-term predator stimuli. However, the causes of predatorinduced weight regulation are highly variable and the underlying mechanisms remain unclear. Understanding this phenomenon is important for gaining a better understanding of how animals regulate body weight under ethologically relevant conditions and has implications for obesity. Here we expose inbred C57BL/6J mice to a fearinducing odorant (2,4,5-trimethylthiazole; mT) to model predation-induced weight regulation. Eight week-old mice were put on a 45% high fat diet (HFD) or chow diet (5% fat) and exposed daily to mT, an equally aversive dose of butyric acid (BA), or a neutral control scent (almond). mT-exposed mice in both diet groups gained significantly less weight over a 6-week period than BA-exposed mice. This differential weight gain appears unlikely to be due to differences in food intake and activity level, or brown adipose thermogenesis between the mT and BA groups. However, following chronic mT exposure we find increases in ΔFosB protein, a marker for long-term neural plasticity, in the dorsomedial hypothalamus (DMH)--an area previously implicated in chronic stress and defensive responses, as well as weight regulation. This study establishes a simplified and robust laboratory model of predation-mediated weight regulation with inbred lab mice and fear-inducing odor, and suggests a likely, yet undetermined, metabolic adaptation as contributing to this response. [ABSTRACT FROM AUTHOR]

Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ∆FosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration, all behavioral findings consistent with the enrichment phenotype. In contrast, however, ∆FosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, accumulation of ΔFosB in NAc shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment.

While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.