WIN55,212-2, a cannabinoid receptors agonist, attenuates the short and long-term behavioural and neuroinflammatory changes induced by repeated social defeat stress in mice

Exposure to stress may contribute to enhanced vulnerability to drug use disorders, by altering sensitivity to drug-related reward and psychomotor effects. This study aimed to characterize the psychomotor effects of nicotine administration and then investigate the consequences of two types of repeated social defeat stress (episodic and continuous) on nicotine-induced psychomotor effects in mice. Adult male Swiss mice were treated for 13 days with daily injections of nicotine (0.1, 0.4, or 1.0 mg/kg, s.c.) and received saline and nicotine challenges (0, 0.1 and 0.4 mg/kg) after a withdrawal period. Dose-dependent effects were observed in locomotor response to nicotine, with trends for locomotor stimulation after intermittent (but not acute) administration of 0.1 mg/kg. Higher nicotine doses caused acute locomotor suppression (0.4 and 1.0 mg/kg) and tolerance after intermittent administration (0.4 mg/kg dose). In separate cohorts, experimental mice were daily defeated by aggressive mice, using the resident-intruder model, for 10 days. After brief confrontations, intruders returned to their home cage (episodic stress) or were continuously exposed to the aggressive resident for 24 h (continuous stress), until the following defeat. After the 10-day stress protocol, mice received saline and nicotine challenges (0 and 0.1 mg/kg, s.c.) in locomotor tests. Mice were also tested for methamphetamine-induced locomotor response (1.0 mg/kg, i.p.). Both defeat protocols induced short-term locomotor suppression (24h after stress), which was further suppressed by nicotine only in mice exposed to continuous defeat stress. Ten days after stress, locomotor behavior was no longer suppressed in defeated mice of either stress protocol. Mice exposed to continuous defeat stress showed a reduced stimulant response to methamphetamine, 12 days after termination of stress. Our findings indicate that exposure to continuous defeat stress facilitates nicotine-induced locomotor suppression shortly after stress and reduces methamphetamine-induced stimulation in the long term.

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Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning

eLife ◽

10.7554/elife.15448 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 24

Author(s):

Claire E Stelly ◽

Matthew B Pomrenze ◽

Jason B Cook ◽

Hitoshi Morikawa

Keyword(s):

Social Defeat ◽

Long Term Potentiation ◽

Receptor Activation ◽

Place Conditioning ◽

Contextual Cues ◽

Social Defeat Stress ◽

Repeated Stress ◽

Term Potentiation ◽

Stressful Experiences

Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca2+ signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences.

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The Long-Term Effects of Adolescent Social Defeat Stress on Oligodendrocyte Lineage Cells and Neuroinflammatory Mediators in Mice

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s247497 ◽

2020 ◽

Vol Volume 16 ◽

pp. 1321-1330

Author(s):

Yingjuan Xu ◽

Zeman Fang ◽

Cairu Wu ◽

Haiyun Xu ◽

Jiming Kong ◽

...

Keyword(s):

Social Defeat ◽

Long Term Effects ◽

Social Defeat Stress

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Chronic Social Defeat During Adolescence Induces Short- and Long-Term Behavioral and Neuroendocrine Effects in Male Swiss-Webster Mice

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.734054 ◽

2021 ◽

Vol 15 ◽

Author(s):

Héctor Miguel Mancha-Gutiérrez ◽

Erika Estrada-Camarena ◽

Lilian Mayagoitia-Novales ◽

Elena López-Pacheco ◽

Carolina López-Rubalcava

Keyword(s):

Early Adolescence ◽

Cognitive Deficits ◽

Early Adulthood ◽

Social Defeat ◽

Adolescent Male ◽

Normal Brain ◽

Dependent Manner ◽

Barnes Maze ◽

Short And Long Term

Chronic stress exposure during adolescence is a significant risk factor for the development of depression. Chronic social defeat (CSD) in rodents is an animal model of depression with excellent ethological, predictive, discriminative, and face validity. Because the CSD model has not been thoroughly examined as a model of stress-induced depression within the adolescence stage, the present study analyzed the short- and long-term behavioral and neuroendocrine effects of CSD during early adolescence. Therefore, adolescent male Swiss-Webster (SW) mice were exposed to the CSD model from postnatal day (PND) 28 to PND37. Twenty-four hours (mid-adolescence) or 4 weeks (early adulthood) later, mice were tested in two models of depression; the social interaction test (SIT) and forced swimming test (FST); cognitive deficits were evaluated in the Barnes maze (BM). Finally, corticosterone and testosterone content was measured before, during, and after CSD exposure, and serotonin transporter (SERT) autoradiography was studied after CSD in adolescent and adult mice. CSD during early adolescence induced enduring depression-like behaviors as inferred from increased social avoidance and immobility behavior in the SIT and FST, respectively, which correlated in an age-dependent manner with SERT binding in the hippocampus; CSD during early adolescence also induced long-lasting learning and memory impairments in the Barnes maze (BM). Finally, CSD during early adolescence increased serum corticosterone levels in mid-adolescence and early adulthood and delayed the expected increase in serum testosterone levels observed at this age. In conclusion: (1) CSD during early adolescence induced long-lasting depression-like behaviors, (2) sensitivity of SERT density during normal brain development was revealed, (3) CSD during early adolescence induced enduring cognitive deficits, and (4) results highlight the vulnerability of the adolescent brain to social stressors on the adrenal and gonadal axes, which emphasizes the importance of an adequate interaction between both axes during adolescence for normal development of brain and behavior.

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Viral depletion of VTA BDNF in rats modulates social behavior, consequences of intermittent social defeat stress, and long-term weight regulation

Neuroscience Letters ◽

10.1016/j.neulet.2011.07.043 ◽

2011 ◽

Vol 502 (3) ◽

pp. 192-196 ◽

Cited By ~ 20

Author(s):

Sanya Fanous ◽

Ernest F. Terwilliger ◽

Ronald P. Hammer Jr. ◽

Ella M. Nikulina

Keyword(s):

Social Behavior ◽

Social Defeat ◽

Weight Regulation ◽

Social Defeat Stress

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Cannabis Hyperemesis Syndrome: A Still Under-Recognized Syndrome

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_001588 ◽

2020 ◽

Author(s):

Attout Hassene ◽

Amichi Sofia ◽

Josse Françoise ◽

Appavoupoule Vincent ◽

Randriajohany Andrey ◽

...

Keyword(s):

Illicit Drugs ◽

Cannabinoid Receptors ◽

Inhibitory Effect ◽

Nausea And Vomiting ◽

Cannabinoid Hyperemesis Syndrome ◽

Short And Long Term ◽

Emergency Room Care ◽

Impaired Attention

Cannabis is one of the most widely used illicit drugs in the world. Its use is associated with several short- and long-term side-effects such as changes in mood, impaired memory, impaired attention, depression and anxiety, and it is correlated with schizophrenia. Cannabinoid hyperemesis syndrome (CHS) is characterized by chronic cannabis use, cyclic intractable nausea and vomiting, and compulsive hot bathing. Patients are typically diagnosed with CHS only after multiple medical evaluations. Recent research has identified type 1 cannabinoid receptors in the intestinal nerve plexus that have an inhibitory effect on gastrointestinal motility. This effect may explain hyperemesis in cannabis users. The thermoregulatory role of endocannabinoids may be responsible for compulsive hot bathing. We describe the cases of two young men seeking repeated emergency room care with recurrent nausea and vomiting. Abstinence from cannabis led to resolution of vomiting symptoms and abdominal pain.

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