Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats.

paper Cited Public

Authors: Sciolino, N R; Bortolato, M; Eisenstein, S A; Fu, J; Oveisi, F; Hohmann, A G; Piomelli, D
Year: 2010
Journal: Neuroscience
PMID: 20394803
DOI: 10.1016/j.neuroscience.2010.04.007
PMCID: PMC2882942

Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced changes in endocannabinoid content (piriform, prefrontal cortices), compared to group-reared rats. Our findings suggest alterations in the endocannabinoid system may contribute to the abnormal isolate phenotype. Handling modifies the endocannabinoid system and behavioral reactivity to context, but surmounts only some effects of social isolation. These data implicate a pivotal role for the endocannabinoid system in stress adaptation and emotionality-related disturbances.

#	Section	Preview
40	DISCUSSION — Chronic handling alters the endocannabinoid system in a region and ligand specific manner	Chronic handling produced stable changes in the endocannabinoid signaling system in both Papez…
41	DISCUSSION — Chronic handling alters the endocannabinoid system in a region and ligand specific manner	increased anandamide levels observed in non-handled isolates. Our data are consistent with the…
42	DISCUSSION — Chronic handling alters the endocannabinoid system in a region and ligand specific manner	Handling increased cannabinoid receptor densities in the limbic loop of the basal ganglia, including…
43	DISCUSSION — Chronic handling alters the endocannabinoid system in a region and ligand specific manner	Supporting this hypothesis, both acute handling (Korz and Frey, 2003) and social isolation (Lu et…
44	DISCUSSION — Chronic handling alters the endocannabinoid system in a region and ligand specific manner	In socially isolated rats, chronic experimenter handling was not sufficient to modify cannabinoid…
45	CONCLUSION	The present report demonstrates that post-weaning social isolation alters principal components of…

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In this knowledge base

Title	Year	PMID
Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.	2015	26595473

External

Title	Authors	Journal	Year	Link
A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.	Borland JM	—	2025	→
Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions.	Rosa I et al.	—	2025	→
Genetic deletion of NAPE-PLD alters stress responsiveness and HPA-axis functionality in a context-dependent manner in mice.	Woodward TJ et al.	—	2025	→
The Role of Fatty Acid Binding Proteins in Neuropsychiatric Diseases: A Narrative Review.	Powell A et al.	—	2025	→
Biomarkers of stress resilience: A review.	Paribello P et al.	—	2024	→
Effects of short-term isolation on social behaviors in prairie voles.	Madrid JE et al.	—	2024	→
Fatty acid binding protein 7 plays an important modulatory sex-dependent role on brain endocannabinoid levels and THC metabolism.	Penman SL et al.	—	2024	→
How depression and antidepressant drugs affect endocannabinoid system?-review of clinical and preclinical studies.	Dragon J et al.	—	2024	→
Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation - Relevance to psychiatric and neurodevelopmental illness, and implications for treatment.	Goh JY et al.	—	2024	→
Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.	Inserra A et al.	—	2023	→
FABP5 is important for cognitive function and is an important regulator of the physiological effects and pharmacokinetics of acute Δ9 tetrahydrocannabinol inhalation in mice.	Penman SL et al.	—	2023	→
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation.	Perini I et al.	—	2023	→
Social isolation leads to mild social recognition impairment and losses in brain cellularity.	Guimarães DM et al.	—	2023	→
Autism and associated disorders: cannabis as a potential therapy.	Babayeva M et al.	—	2022	→
De-risking in Tier I CNS safety assessments is the primary function of study design and technical training of laboratory staff observers.	Gauvin DV et al.	—	2022	→
Dynamic influences on the neural encoding of social valence.	Padilla-Coreano N et al.	—	2022	→
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation.	Perini I et al.	—	2022	—
Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats.	Bijlsma A et al.	—	2022	→
Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation?	Mayo LM et al.	—	2022	→
Acute cannabidiol treatment attenuates ethanol-induced place preference and reduces aggressivity in group-housed male rats.	Andaloussi ZL et al.	—	2021	→
A novel social fear conditioning procedure alters social behavior and mTOR signaling in differentially housed adolescent rats.	Dawud LM et al.	—	2021	→
Early life stress and development of the endocannabinoid system: A bidirectional process in programming future coping.	Goldstein Ferber S et al.	—	2021	→
Effect of chronic handling and social isolation on emotion and cognition in adolescent rats.	Song MK et al.	—	2021	→
Lifestyle Interventions Improving Cannabinoid Tone During COVID-19 Lockdowns May Enhance Compliance With Preventive Regulations and Decrease Psychophysical Health Complications.	Brugnatelli V et al.	—	2021	→
Sex- and context-dependent effects of acute isolation on vocal and non-vocal social behaviors in mice.	Zhao X et al.	—	2021	→
The neural circuitry of social homeostasis: Consequences of acute versus chronic social isolation.	Lee CR et al.	—	2021	→
CB<sub>1</sub> Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study.	Laricchiuta D et al.	—	2020	→
The globus pallidus as a target for neuropeptides and endocannabinoids participating in central activities.	Chen XY et al.	—	2020	→
Cannabidivarin completely rescues cognitive deficits and delays neurological and motor defects in male <i>Mecp2</i> mutant mice.	Zamberletti E et al.	—	2019	→
Neurobiology and consequences of social isolation stress in animal model-A comprehensive review.	Mumtaz F et al.	—	2018	→
Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress.	Haj-Mirzaian A et al.	—	2017	→
Cannabidiol-Δ<sup>9</sup>-tetrahydrocannabinol interactions on acute pain and locomotor activity.	Britch SC et al.	—	2017	→
Chronic stress and hippocampal dendritic complexity: Methodological and functional considerations.	Conrad CD et al.	—	2017	→
Endocannabinoid Signaling in the Control of Social Behavior.	Wei D et al.	—	2017	→
Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: Effect of isolation rearing.	Minami C et al.	—	2017	→
Perspectives on the Role of Endocannabinoids in Autism Spectrum Disorders.	Yeh ML et al.	—	2017	→
Adverse Social Experiences in Adolescent Rats Result in Enduring Effects on Social Competence, Pain Sensitivity and Endocannabinoid Signaling.	Schneider P et al.	—	2016	→
BDNF-Val66Met variant and adolescent stress interact to promote susceptibility to anorexic behavior in mice.	Madra M et al.	—	2016	→
Emotional arousal state influences the ability of amygdalar endocannabinoid signaling to modulate anxiety.	Morena M et al.	—	2016	→
Endocannabinoid signaling in social functioning: an RDoC perspective.	Karhson DS et al.	—	2016	→
Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment.	Wei D et al.	—	2016	→
Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history.	Dow-Edwards D et al.	—	2016	→
Blockade of NMDA receptors reverses the depressant, but not anxiogenic effect of adolescence social isolation in mice.	Haj-Mirzaian A et al.	—	2015	→
Endocannabinoid Signaling in Autism.	Chakrabarti B et al.	—	2015	→
Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis.	Carey CE et al.	—	2015	→
A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior.	McLaughlin RJ et al.	—	2014	→
Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system.	McPartland JM et al.	—	2014	→
Stress regulates endocannabinoid-CB1 receptor signaling.	Hillard CJ	—	2014	→
Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation.	Hori M et al.	—	2014	→
Cannabinoids and glucocorticoids modulate emotional memory after stress.	Akirav I	—	2013	→
Effects of repeated tickling on conditioned fear and hormonal responses in socially isolated rats.	Hori M et al.	—	2013	→
The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex.	Fitzgerald ML et al.	—	2013	→
Antagonism of cannabinoid 1 receptors reverses the anxiety-like behavior induced by central injections of corticotropin-releasing factor and cocaine withdrawal.	Kupferschmidt DA et al.	—	2012	→
A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.	Lim AL et al.	—	2012	→
Chronic blockade of CB(1) receptors reverses startle gating deficits and associated neurochemical alterations in rats reared in isolation.	Zamberletti E et al.	—	2012	→
Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?	Hall FS et al.	—	2012	→
Long-lasting recovery of psychotic-like symptoms in isolation-reared rats after chronic but not acute treatment with the cannabinoid antagonist AM251.	Zamberletti E et al.	—	2012	→
Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment.	Edmiston EE et al.	—	2011	→
Differential sensitivity to amphetamine's effect on open field behavior of psychosocially stressed male rats.	Pohorecky LA et al.	—	2011	→
Endocannabinoid system and psychiatry: in search of a neurobiological basis for detrimental and potential therapeutic effects.	Marco EM et al.	—	2011	→
Enhancement of endocannabinoid signaling with JZL184, an inhibitor of the 2-arachidonoylglycerol hydrolyzing enzyme monoacylglycerol lipase, produces anxiolytic effects under conditions of high environmental aversiveness in rats.	Sciolino NR et al.	—	2011	→
Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis.	Bortolato M et al.	—	2010	→