Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure

Autor: Ramesh Chittajallu, Calvin Fang, Xiaoqing Yuan, Chris J. McBain, Geoffrey A. Vargish, David P. Collins, Kenneth A. Pelkey
Rok vydání: 2015
Předmět:
0301 basic medicine
Agonist
Nervous system
medicine.medical_specialty
medicine.drug_class
Offspring
medicine.medical_treatment
Morpholines
Naphthalenes
Inhibitory postsynaptic potential
Hippocampus
Nervous System
Article
03 medical and health sciences
Cellular and Molecular Neuroscience
Mice
0302 clinical medicine
Receptor
Cannabinoid
CB1
Interneurons
Pregnancy
Internal medicine
medicine
Animals
Dronabinol
Receptors
Cannabinoid
Social Behavior
Molecular Biology
Cannabis
Fetus
Cannabinoids
digestive
oral
and skin physiology
medicine.disease
Benzoxazines
Mice
Inbred C57BL
Psychiatry and Mental health
030104 developmental biology
medicine.anatomical_structure
Endocrinology
In utero
Prenatal Exposure Delayed Effects
Female
Cannabinoid
Psychology
Cholecystokinin
Neuroscience
030217 neurology & neurosurgery
Endocannabinoids
Zdroj: Molecular psychiatry
ISSN: 1476-5578
Popis: Placental transfer of Δ9-tetrahydrocannabinol (THC) during pregnancy has the potential to interfere with endogenous cannabinoid regulation of fetal nervous system development in utero. Here we examined the effect of maternal cannabinoid intake on mouse hippocampal interneurons largely focusing on cholecystokinin containing interneurons (CCK-INTs), a prominent cannabinoid subtype 1 receptor (CB1R) expressing neuronal population throughout development. Maternal treatment with THC or the synthetic CB1R agonist WIN55,212-2 (WIN) produced a significant loss of CCK-INTs in offspring. Further, residual CCK-INTs in animals prenatally treated with WIN displayed decreased dendritic complexity. Consistent with these anatomical deficits, pups born to cannabinoid treated dams exhibited compromised CCK-INT mediated feedforward and feedback inhibition. Moreover, pups exposed to WIN in utero lacked constitutive CB1R mediated suppression of inhibition from residual CCK-INTs, and displayed altered social behavior. Our findings add to a growing list of potential cell/circuit underpinnings that may underlie cognitive impairments in offspring of mothers that abuse marijuana during pregnancy.
Databáze: OpenAIRE
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