Skip to main content
Article
L-theanine prevents long-term affective and cognitive side effects of adolescent Δ-9-tetrahydrocannabinol exposure and blocks associated molecular and neuronal abnormalities in the mesocorticolimbic circuitry
Journal of Neuroscience
  • Marta De Felice, Schulich School of Medicine & Dentistry
  • Justine Renard, Schulich School of Medicine & Dentistry
  • Roger Hudson, Schulich School of Medicine & Dentistry
  • Hanna J. Szkudlarek, Schulich School of Medicine & Dentistry
  • Brian J. Pereira, Schulich School of Medicine & Dentistry
  • Susanne Schmid, University of Western Ontario
  • Walter J. Rushlow, Schulich School of Medicine & Dentistry
  • Steven R. Laviolette, Schulich School of Medicine & Dentistry
Document Type
Article
Publication Date
1-27-2021
URL with Digital Object Identifier
10.1523/JNEUROSCI.1050-20.2020
Disciplines
Abstract

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. L-Theanine is an amino acid analog of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exposure in male rats, we report that L-theanine pretreatment before adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect that persists into adulthood. In addition, pretreatment with L-theanine blocked THC-induced downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and subcortical DAergic dysregulation. Finally, L-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of L-theanine in the mesocorticolimbic system.

Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Marta De Felice, Justine Renard, Roger Hudson, Hanna J. Szkudlarek, et al.. "L-theanine prevents long-term affective and cognitive side effects of adolescent Δ-9-tetrahydrocannabinol exposure and blocks associated molecular and neuronal abnormalities in the mesocorticolimbic circuitry" Journal of Neuroscience Vol. 41 Iss. 4 (2021) p. 739 - 750
Available at: http://works.bepress.com/susanne-schmid/30/