Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex.
Tiziana Rubino, Pamela Prini, Fabiana Piscitelli, Erica Zamberletti, Massimo Trusel, Miriam Melis, Claudia Sagheddu, A. Ligresti, Raffaella Tonini, Vincenzo Di Marzo, Daniela Parolaro
Neurobiology of Disease 2015 DOI: 10.1016/j.nbd.2014.09.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Female rats exposed to THC during adolescence |
| Intervention | THC |
| Topics | Cannabis |
| Key points | Adolescent THC exposure in female rats disrupted endocannabinoid system maturation in the prefrontal cortex, impairing endocannabinoid signaling and endocannabinoid-mediated LTD in adulthood, altering NMDA subunit levels (more gluN2B) and AMPA gluA1, and changing adult cognition. Blocking CB1 receptors during adolescence appeared to prevent pruning at glutamatergic synapses. The authors propose that lasting THC vulnerability may partly reside in disruption of the endocannabinoid system's role in prefrontal cortex maturation. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- The CannTeen Study: Verbal Episodic Memory, Spatial Working Memory, and Response Inhibition in Adolescent and Adult Cannabis Users and Age-Matched Controls PRE-PRINT February 18, 2022
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Cites 8
- Alterations of prefrontal cortex GABAergic transmission in the complex psychotic-like phenotype induced by adolescent delta-9-tetrahydrocannabinol exposure in rats. Neurobiology of Disease March 1, 2014
- SK channel modulation rescues striatal plasticity and control over habit in cannabinoid tolerance. Nature Neuroscience January 8, 2012
- Chronic URB597 treatment at adulthood reverted most depressive-like symptoms induced by adolescent exposure to THC in female rats. Neuropharmacology 2011
- Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Progress in Neurobiology November 2010
- Changes in hippocampal morphology and neuroplasticity induced by adolescent THC treatment are associated with cognitive impairment in adulthood. Hippocampus August 2009
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