Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex
Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure...
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doaj-6a1348f21c2f49ea9faf71f6eb9516972021-03-22T12:41:57ZengElsevierNeurobiology of Disease1095-953X2015-01-01736069Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortexTiziana Rubino0Pamela Prini1Fabiana Piscitelli2Erica Zamberletti3Massimo Trusel4Miriam Melis5Claudia Sagheddu6Alessia Ligresti7Raffaella Tonini8Vincenzo Di Marzo9Daniela Parolaro10Department of Theoretical and Applied Science, Biomedical Research Division, and Neuroscience Center, University of Insubria, 21052 Busto Arsizio, VA, Italy; Corresponding author: Department of Theoretical and Applied Science, Biomedical Research Division, Neuroscience Center, University of Insubria, via Manara 7, 21052 Busto Arsizio (VA), Italy. Tel.: +39 0331339416; fax: +39 0331339459.Department of Theoretical and Applied Science, Biomedical Research Division, and Neuroscience Center, University of Insubria, 21052 Busto Arsizio, VA, ItalyEndocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, 80078 Pozzuoli, NA, ItalyDepartment of Theoretical and Applied Science, Biomedical Research Division, and Neuroscience Center, University of Insubria, 21052 Busto Arsizio, VA, ItalyDepartment of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia (IIT), 16163 Genova, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, CA, ItalyDepartment of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042 Monserrato, CA, ItalyEndocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, 80078 Pozzuoli, NA, ItalyDepartment of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia (IIT), 16163 Genova, ItalyEndocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, 80078 Pozzuoli, NA, ItalyDepartment of Theoretical and Applied Science, Biomedical Research Division, and Neuroscience Center, University of Insubria, 21052 Busto Arsizio, VA, Italy; Zardi Gori Foundation, 21100 Milan, ItalyCurrent concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation.http://www.sciencedirect.com/science/article/pii/S0969996114002873Endocannabinoid systemAdolescencePrefrontal cortexNMDA receptorsAMPA receptorsSpine density |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tiziana Rubino Pamela Prini Fabiana Piscitelli Erica Zamberletti Massimo Trusel Miriam Melis Claudia Sagheddu Alessia Ligresti Raffaella Tonini Vincenzo Di Marzo Daniela Parolaro |
spellingShingle |
Tiziana Rubino Pamela Prini Fabiana Piscitelli Erica Zamberletti Massimo Trusel Miriam Melis Claudia Sagheddu Alessia Ligresti Raffaella Tonini Vincenzo Di Marzo Daniela Parolaro Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex Neurobiology of Disease Endocannabinoid system Adolescence Prefrontal cortex NMDA receptors AMPA receptors Spine density |
author_facet |
Tiziana Rubino Pamela Prini Fabiana Piscitelli Erica Zamberletti Massimo Trusel Miriam Melis Claudia Sagheddu Alessia Ligresti Raffaella Tonini Vincenzo Di Marzo Daniela Parolaro |
author_sort |
Tiziana Rubino |
title |
Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex |
title_short |
Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex |
title_full |
Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex |
title_fullStr |
Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex |
title_full_unstemmed |
Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex |
title_sort |
adolescent exposure to thc in female rats disrupts developmental changes in the prefrontal cortex |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2015-01-01 |
description |
Current concepts suggest that exposure to THC during adolescence may act as a risk factor for the development of psychiatric disorders later in life. However, the molecular underpinnings of this vulnerability are still poorly understood. To analyze this, we investigated whether and how THC exposure in female rats interferes with different maturational events occurring in the prefrontal cortex during adolescence through biochemical, pharmacological and electrophysiological means. We found that the endocannabinoid system undergoes maturational processes during adolescence and that THC exposure disrupts them, leading to impairment of both endocannabinoid signaling and endocannabinoid-mediated LTD in the adult prefrontal cortex. THC also altered the maturational fluctuations of NMDA subunits, leading to larger amounts of gluN2B at adulthood. Adult animals exposed to THC during adolescence also showed increased AMPA gluA1 with no changes in gluA2 subunits. Finally, adolescent THC exposure altered cognition at adulthood. All these effects seem to be triggered by the disruption of the physiological role played by the endocannabinoid system during adolescence. Indeed, blockade of CB1 receptors from early to late adolescence seems to prevent the occurrence of pruning at glutamatergic synapses. These results suggest that vulnerability of adolescent female rats to long-lasting THC adverse effects might partly reside in disruption of the pivotal role played by the endocannabinoid system in the prefrontal cortex maturation. |
topic |
Endocannabinoid system Adolescence Prefrontal cortex NMDA receptors AMPA receptors Spine density |
url |
http://www.sciencedirect.com/science/article/pii/S0969996114002873 |
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