Effects of conditioned social fear on ethanol drinking and vice-versa in male mice

2019

J Psychopharmacol

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Background: Neuropeptide Y (NPY) has anxiolytic effects and facilitates extinction of cued and contextual fear in rodents, thereby acting as a resilience factor against exaggerated fear responses after adverse events. We investigated whether NPY influences acquisition, expression and extinction of social fear in a mouse model of social fear conditioning (SFC). Methods: NPY was administered intracerebroventricularly before SFC or before social fear extinction with or without prior administration of Y1 and/or Y2 receptor antagonists. Results: We show that NPY affects SFC-induced social fear in a time point–dependent manner. When administered before SFC, NPY did not affect acquisition, expression and extinction of social fear. However, when administered before social fear extinction, NPY reduced expression of social fear via simultaneous activation of Y1 and Y2 receptors. As such, neither the Y1 receptor antagonist BIBO3304 trifluoroacetate nor the Y2 receptor antagonist BIIE0246 was able to block the effects of NPY completely. However, when administered in combination, they completely blocked the effects of NPY on social fear expression. Conclusions: These findings have important clinical implications, as they suggest that although medication strategies aimed at increasing brain NPY activity are unlikely to prevent the formation of aversive memories after a traumatic social experience, they might improve the recovery from a traumatic social experience by reducing the expression of social fear.

Section: Methodsmentioning

confidence: 99%

Neuropeptide Y reduces expression of social fear via simultaneous activation of Y1 and Y2 receptors

2019

J Psychopharmacol

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“…Interestingly, all control SFC + mice (i.e., water-drinking and vehicle-treated) used in this study failed to show extinction of social fear, i.e., a gradual decrease in social fear as a result of repeated exposure to social stimuli. Gradual social fear extinction has been previously described in untreated and vehicle-treated CD1 mice [22,23,[34][35][36][37][38][39] and is similar to the outcome during exposure therapy in SAD patients [2]. This difference in social fear extinction might arise from potential genetic-related strain differences.…”

Section: Discussionmentioning

confidence: 54%

“…These strain differences in social behavior were not only observed in SFC + mice but, also, in SFC − mice, i.e., SFC − ASM+/+, ASM+/−, and ASM−/− mice showed lower levels of social investigation during social fear extinction compared with SFC − CD1 mice. SFC − CD1 mice usually spend around 80% of the time investigating the social stimuli [22,23,[34][35][36][37][38][39] and show high levels of aggressive behavior, whereas SFC − C57BL/6 mice used in this study spent around 60% of the time investigating the social stimuli and showed no aggressive behavior.…”

Section: Discussionmentioning

confidence: 83%

“…SFC. SFC was performed with a computerized fear conditioning system (TSE System GmbH, Bad Homburg, Germany), as previously described [22,29,[34][35][36][37][38][39] (see [24] for a schematic representation of the SFC paradigm). Mice were placed in the conditioning chamber (45 × 22 × 40 cm), and after a 30-sec habituation period, an empty wire mesh cage (7 × 7 × 6 cm) was placed as a non-social stimulus near one of the short walls.…”

Section: Social Fear Conditioning (Sfc) Paradigmmentioning

confidence: 99%

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Neuropeptide Y as Alternative Pharmacotherapy for Antidepressant-Resistant Social Fear

2020

IJMS

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In many social anxiety disorder (SAD) patients, the efficacy of antidepressant therapy is unsatisfactory. Here, we investigated whether mice deficient for the lysosomal glycoprotein acid sphingomyelinase (ASM−/−) represent an appropriate tool to study antidepressant-resistant social fear. We also investigated whether neuropeptide Y (NPY) reduces this antidepressant-resistant social fear in ASM−/− mice, given that NPY reduced social fear in a mouse model of SAD, namely social fear conditioning (SFC). We show that neither chronic paroxetine nor chronic amitriptyline administration via drinking water were successful in reducing SFC-induced social fear in ASM−/− mice, while the same treatment reduced social fear in ASM+/− mice and completely reversed social fear in ASM+/+ mice. This indicates that the antidepressants paroxetine and amitriptyline reduce social fear via the ASM-ceramide system and that ASM−/− mice represent an appropriate tool to study antidepressant-resistant social fear. The intracerebroventricular administration of NPY, on the other hand, reduced social fear in ASM−/− mice, suggesting that NPY might represent an alternative pharmacotherapy for antidepressant-resistant social fear. These results suggest that medication strategies aimed at increasing brain NPY concentrations might improve symptoms of social fear in SAD patients who fail to respond to antidepressant treatments.

“…SFC. SFC was performed with a computerized fear conditioning system (TSE System GmbH, Bad Homburg, Germany) as previously described [ 21 , 22 , 23 , 24 , 35 , 36 , 37 , 38 ]. Mice were placed in the conditioning chamber (45 × 22 × 40 cm) and, after a 30-s habituation period, an empty wire mesh cage (7 × 7 × 6 cm) was placed as a non-social stimulus near one of the short walls.…”

Section: Methodsmentioning

confidence: 99%

Social Fear Memory Requires Two Stages of Protein Synthesis in Mice

2020

IJMS

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It is well known that long-term consolidation of newly acquired information, including information related to social fear, require de novo protein synthesis. However, the temporal dynamics of protein synthesis during the consolidation of social fear memories is unclear. To address this question, mice received a single systemic injection with the protein synthesis inhibitor, anisomycin, at different time-points before or after social fear conditioning (SFC), and memory was assessed 24 h later. We showed that anisomycin impaired the consolidation of social fear memories in a time-point-dependent manner. Mice that received anisomycin 20 min before, immediately after, 6 h, or 8 h after SFC showed reduced expression of social fear, indicating impaired social fear memory, whereas anisomycin caused no effects when administered 4 h after SFC. These results suggest that consolidation of social fear memories requires two stages of protein synthesis: (1) an initial stage starting during or immediately after SFC, and (2) a second stage starting around 6 h after SFC and lasting for at least 5 h.