TY - JOUR T1 - The same stress has divergent effects on social versus asocial manifestations of anxiety-like behavior over time. JF - Stress Y1 - 2021 A1 - Saxena, Kapil A1 - Chakraborty, Prabahan A1 - Chattarji, Sumantra KW - Amygdala KW - Animals KW - Anxiety KW - Anxiety Disorders KW - Behavior, Animal KW - Disease Models, Animal KW - Male KW - Rats KW - Social Behavior KW - Stress, Psychological AB -

Stress may lead to augmented anxiety, which may, with time culminate in some form of anxiety disorder. Behavioral alterations related to increased anxiety can be broadly classified into two types-social, affecting interactions between individuals, and self-oriented, affecting the anxious individual only. While a growing body of literature now exists describing the effects of stress-induced anxiety on self-oriented behavior in animal models of anxiety disorders, the effects of such aberrant anxiety on social behavior has largely remained uncharacterized in these models. This study aims to fill this gap in our understanding by examining changes in social behavior following a single 2-hour episode of immobilization stress, which has been shown to cause delayed structural and functional changes in the amygdala. To this end, we examined social behavior, measured as active social interactions, anogenital sniffing, nose-to-nose contacts, allogrooming, actively following and crawling under, as well as self-oriented asocial behavior, manifested as self-grooming and rearing, in adult male rats. Stressed animals showed reduced social interaction 1 day after immobilization stress and this decrease was persistent for at least 10 days after stress. In contrast, individualistic behaviors were impaired only 10 days, but not 1 day later. Together, these results not only show that the same single episode of stress can elicit divergent effects on social and asocial measures of anxiety in the same animal, but also suggest that enhanced social anxiety soon after stress may also serve as an early indicator of its delayed behavioral effects.

VL - 24 IS - 4 ER - TY - JOUR T1 - Stress-induced modulation of endocannabinoid signaling leads to delayed strengthening of synaptic connectivity in the amygdala. JF - Proc Natl Acad Sci U S A Y1 - 2020 A1 - Yasmin, Farhana A1 - Colangeli, Roberto A1 - Morena, Maria A1 - Filipski, Sarah A1 - van der Stelt, Mario A1 - Pittman, Quentin J A1 - Hillard, Cecilia J A1 - Teskey, G Campbell A1 - McEwen, Bruce S A1 - Hill, Matthew N A1 - Chattarji, Sumantra KW - Administration, Oral KW - Amidohydrolases KW - Animals KW - Basolateral Nuclear Complex KW - Cannabinoid Receptor Antagonists KW - Disease Models, Animal KW - Emotions KW - Endocannabinoids KW - Enzyme Inhibitors KW - Excitatory Postsynaptic Potentials KW - Humans KW - Male KW - Rats KW - Receptor, Cannabinoid, CB1 KW - Signal Transduction KW - Stress, Psychological AB -

Even a brief exposure to severe stress strengthens synaptic connectivity days later in the amygdala, a brain area implicated in the affective symptoms of stress-related psychiatric disorders. However, little is known about the synaptic signaling mechanisms during stress that eventually culminate in its delayed impact on the amygdala. Hence, we investigated early stress-induced changes in amygdalar synaptic signaling in order to prevent its delayed effects. Whole-cell recordings in basolateral amygdala (BLA) slices from rats revealed higher frequency of miniature excitatory postsynaptic currents (mEPSCs) immediately after 2-h immobilization stress. This was replicated by inhibition of cannabinoid receptors (CBR), suggesting a role for endocannabinoid (eCB) signaling. Stress also reduced -arachidonoylethanolamine (AEA), an endogenous ligand of CBR. Since stress-induced activation of fatty acid amide hydrolase (FAAH) reduces AEA, we confirmed that oral administration of an FAAH inhibitor during stress prevents the increase in synaptic excitation in the BLA soon after stress. Although stress also caused an immediate reduction in synaptic inhibition, this was not prevented by FAAH inhibition. Strikingly, FAAH inhibition during the traumatic stressor was also effective 10 d later on the delayed manifestation of synaptic strengthening in BLA neurons, preventing both enhanced mEPSC frequency and increased dendritic spine-density. Thus, oral administration of an FAAH inhibitor during a brief stress prevents the early synaptic changes that eventually build up to hyperexcitability in the amygdala. This framework is of therapeutic relevance because of growing interest in targeting eCB signaling to prevent the gradual development of emotional symptoms and underlying amygdalar dysfunction triggered by traumatic stress.

VL - 117 IS - 1 ER - TY - JOUR T1 - Repeated social stress leads to contrasting patterns of structural plasticity in the amygdala and hippocampus. JF - Behav Brain Res Y1 - 2018 A1 - Patel, D A1 - Anilkumar, S A1 - Chattarji, S A1 - Buwalda, B KW - Amygdala KW - Animals KW - Atrophy KW - Avoidance Learning KW - CA1 Region, Hippocampal KW - Dendritic Spines KW - Dominance-Subordination KW - Male KW - Neuronal Plasticity KW - Prefrontal Cortex KW - Pyramidal Cells KW - Rats, Wistar KW - Stress, Psychological AB -

Previous studies have demonstrated that repeated immobilization and restraint stress cause contrasting patterns of dendritic reorganization as well as alterations in spine density in amygdalar and hippocampal neurons. Whether social and ethologically relevant stressors can induce similar patterns of morphological plasticity remains largely unexplored. Hence, we assessed the effects of repeated social defeat stress on neuronal morphology in basolateral amygdala (BLA), hippocampal CA1 and infralimbic medial prefrontal cortex (mPFC). Male Wistar rats experienced social defeat stress on 5 consecutive days during confrontation in the resident-intruder paradigm with larger and aggressive Wild-type Groningen rats. This resulted in clear social avoidance behavior one day after the last confrontation. To assess the morphological consequences of repeated social defeat, 2 weeks after the last defeat, animals were sacrificed and brains were stained using a Golgi-Cox procedure. Morphometric analyses revealed that, compared to controls, defeated Wistar rats showed apical dendritic decrease in spine density on CA1 but not BLA. Sholl analysis demonstrated a significant dendritic atrophy of CA1 basal dendrites in defeated animals. In contrast, basal dendrites of BLA pyramidal neurons exhibited enhanced dendritic arborization in defeated animals. Social stress failed to induce lasting structural changes in mPFC neurons. Our findings demonstrate for the first time that social defeat stress elicits divergent patterns of structural plasticity in the hippocampus versus amygdala, similar to what has previously been reported with repeated physical stressors. Therefore, brain region specific variations may be a universal feature of stress-induced plasticity that is shared by both physical and social stressors.

VL - 347 ER -