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www.nature.com/npp ABSTRACTS COLLECTION ACNP 59th Annual Meeting: Poster Session I Neuropsychopharmacology (2020) 45:68–169; https://doi.org/10.1038/s41386-020-00890-7 Sponsorship Statement: Publication of this supplement is sponsored by the ACNP. Presenting author disclosures may be found within the abstracts. Asterisks in the author lists indicate presenter of the abstract at the annual meeting. M1. Juvenile Social Isolation of Rats Induces Lost of Jessica Jessica Deslauriers*, Jose Figueroa, Cindy Napan, Corticotropin Releasing Factor-Receptor 1 Antagonist Effect in Yanilka Soto-Muniz, Victoria Risbrough the Nucleus Accumbens Université Laval, Québec, Canada Katia Gysling*, Juan Zegers, Javier Novoa, Hector Yarur Background: Post-traumatic stress disorder (PTSD) is a common Pontificia Universidad Catolica de Chile, Santiago, Chile psychiatric condition that is defined by its paradigmatic symptoms including but not limited to anxiety, avoidance, and increased arousal Background: Social isolation is a model of chronic stress widely by environmental cues due to a severely traumatic event. Recent used to study early life adversity. It is well known that early life studies show that this condition is correlated with both peripheral 1234567890();,: adversity may lead to the development of psychiatric disorders in and central immune dysfunction, but the relationship between adulthood. Juvenile rats exposed to social isolation showed inflammation and PTSD remains unclear. In a mouse model of PTSD, increased anxiety-like behavior and significant changes in Nucleus we found increased plasma levels of the pro-inflammatory cytokine Accumbens (Nac) dopamine (DA) activity in adulthood (Lukkes interleukin-1β (IL-1β) after exposure to trauma. A major component in et al. 2009). Interestingly, rats isolated during their juvenile stage the peripheral and central inflammatory pathways is the nucleotide- developed an increase in anxiety-like behavior, but rats isolated binding oligomerization domain-, leucine-rich repeat- and pyrin during their young adult stage showed no effects upon anxiety- domain containing-3 (NLRP3) inflammasome. Since the NLRP3 like behavior (Arakawa, 2003). We are interested in evaluating inflammasome is also known to be a key component in the neuronal changes induced by isolation that could explain the production and release of IL-1β, we hypothesized that the NLRP3 difference between the expression on anxiety like behavior in inflammasome modulates the response to trauma. juvenile and young adult rats. Methods: To test this hypothesis, we exposed a preliminary Methods: We performed in vivo microdialysis to evaluate cohort (n = 8-9 per group/sex) of both male and female wildtype neuronal changes induced by isolation. Prolonged social isolation (WT) and NLRP3 knockout (KO) mice to a predator (cat) stress in an of juvenile rats (10 days) increases DA extracellular level in the Nac enclosed space for 10 minutes. The PTSD-like phenotype was shell. Interestingly, preliminary results showed no difference assessed 1-2 weeks after predator exposure across 3 behavioral between DA extracellular levels in the Nac shell of young adult paradigms: open field, light-dark box, and a trauma-reminder test. isolated and no isolated rats. Next, we evaluated eventual changes A composite avoidance score was then calculated to measure the in corticotropin-releasing factor (CRF) system function induced by overall PTSD-like phenotype. isolation. The CRF system mediates part of the brain stress Results: In all three tests, no effect of genotype was found. In the response. The CRF system is composed by CRF, urocortins, CRF-R1 open field, stress exposure tends to increase PTSD-like phenotype (p and CRF-R2 receptors. = 0.10) in mice, independently of their genotype. In the light-dark Results: Interestingly, the effect of a CRF-R1 antagonist upon box, a main effect of stress was observed (p<0.05), with posthoc DA and glutamate levels in juvenile no isolated rats is occluded comparisons revealing elevated PTSD-like phenotype in stressed KO when rats are isolated. These results suggest that social isolation mice compared to non-stressed KO mice (p<0.05). In the trauma- of juvenile rats decreases CRF-R1 in Nac terminals. Supporting this reminder test, stress tended to exert a main effect (p = 0.10) and to hypothesis, our preliminary results showed that synaptosomes interact with the NLRP3 genotype (p = 0.11). Predator stress tended devoid of postsynaptic elements obtained from the Nac of to increase PTSD-like phenotype in WT, but not KO, mice. isolated juvenile rats have lower number of dots and fluorescence Conclusions: Altogether these preliminary results suggest that intensity of CRF-R1 compared with synaptosomes obtained from the NLRP3 inflammasome may not contribute to the development control not isolated rats. of anxiety-like symptoms, but may modulate the avoidance of Conclusions: Further studies are needed to underlie the cellular trauma-related cues in response to a traumatic event. Additional mechanisms mediating these observed effects. experiments need to be conducted using model to inquire further Keywords: Dopamine, Juvenile Social Isolation, Type 1 Cortico- implications regarding sex-dependent effects of the NLRP3 tropin Releasing Factor Receptor inflammasome in PTSD risk. As current FDA-approved treatments Disclosure: Nothing to disclose. are shown to have a limited efficacy in individuals diagnosed with PTSD, developing an in-depth understanding of the role of these inflammatory signaling pathways in PTSD pathophysiology may M2. The Contribution of the NLRP3 Inflammasome to Trauma be useful for developing novel pharmacological treatments. Response in an Animal Model of PTSD Keywords: PTSD, Inflammasome, Avoidance © The Author(s), under exclusive licence to American College of Neuropsychopharmacology 2020 ACNP 59th Annual Meeting: Poster Session I 69 Disclosure: Nothing to disclose. from the ECM. Stress-CS exposure also induced down-regulation of astroglial glutamate transporters (GLT-1) and retraction of astrocyte synaptic coverage compared to stress animals exposed M3. Glutamatergic Mechanisms Mediate Enduring to a neutral stimulus. Furthermore, we observed differential Vulnerability to Drug Use Following an Acute Stressor changes in Ca2+ activity of D1 vs D2-MSN during restraint stress, defensive burying test and cross-sensitization. Constanza Garcia-Keller*, Ritchy Hoderbourg R, Jordan Carter, Conclusions: These data propose that these changes which Angela M Kearns, Anna Kruyer, Jordan Hopkins, Peter Kalivas, coincide with 15 min defensive burying task seems to be Carmela Reichel correlated with transient synaptic plasticity in NAcore that lead to stress coping responses. Because t-SP is not observed during Medical University of South Carolina, Charleston, South Carolina, cued sucrose seeking, and stress-CS exposure did not induce United States sucrose-seeking in sucrose-trained rats, we hypothesize that the t-SP described here is potentially a pathological feature of stress Background: Converging epidemiological studies indicate that a disorder. Further experiments are needed to establish whether history of acute life-threatening events increases the incidence of stress cue-induced t-SP occur in D1 and whether it correlates with post-traumatic stress disorder (PTSD), and a diagnosis for PTSD changes in Ca2+ activity of D1 or D2-MSN. carries 30–50% comorbidity with substance use disorder (SUDs). Keywords: Post Traumatic Stress Disorder, Tetra Partite Thus, patients with comorbid PTSD/SUDs have greater drug use Synapse, Synaptic Plasticity, Nucleus Accumbens, Substance Use severity and show poorer treatment outcomes than patients Disorder diagnosed with either alone. Using an animal model, we found Disclosure: Nothing to disclose. that exposure to a single stressful event experienced 3 weeks earlier can enhance cocaine, alcohol and heroin intake and trigger a number of enduring adaptations within corticostriatal synapses M4. Parsing Distinct and Common Neural Mechanisms of of the nucleus accumbens core (NAcore), resembling drug Response to Learned Threat in Childhood Anxiety and induced adaptations. Recently, we paired acute restraint stress Irritability with a novel odor and found that stressed rats showed increased reactivity when exposed to a stress-conditioned stimulus (stress- Wan-Ling Tseng*, Rany Abend, Andrea Gold, Melissa Brotman CS) in a defensive burying task and in a self-administration model the stress-CS was sufficient to reinstate cocaine, alcohol and Yale Child Study Center, Yale University School of Medicine, New heroin seeking in extinguished animals. Haven, Connecticut, United States Drug-associated cue presentation evokes transient increases in the tetrapartite synapse, including pre and postsynaptic neurons, Background: Symptomic comorbidity is pervasive in psychiatry. astrocytes and the extracellular matrix (ECM), that coincide with This clinical heterogeneity impedes diagnosis and target 15 min of drug cue-associated exposure. These transient changes identification for the development of precise mechanistic are referred to as transient synaptic plasticity (t-SP) because they treatments. Anxiety and irritability are among the most highly are reversed by 120 min after initiation of the behavior. Given the co-occurring problems in youth (e.g., Shimshoni et al., 2020). overlap between the enduring adaptations produced by acute Children with both elevated irritability and anxiety, compared restraint stress and withdrawal from cocaine
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