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CESARE D'AMICO

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity

  • Autori: Castelli, Valentina; Lavanco, Gianluca; D’Amico, Cesare; Feo, Salvatore; Tringali, Giuseppe; Kuchar, Martin; Cannizzaro, Carla; Brancato, Anna
  • Anno di pubblicazione: 2023
  • Tipologia: Articolo in rivista
  • OA Link: http://hdl.handle.net/10447/603693

Abstract

Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to Δ-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for “brain reprogramming”, we aimed at assessing the role of the nonpsychoactive phytocannabinoid cannabidiol (CBD) as a rescue strategy to temper prenatal THC-induced harm. Methods: To this aim, Wistar rats prenatally exposed to THC (2 mg/kg s.c.) or vehicle (gestational days 5–20) were tested for specific indexes of spatial and configural memory in the reinforcement-motivated Can test and in the aversion-driven Barnes maze test during adolescence. Markers of hippocampal excitatory plasticity and endocannabinoid signaling—NMDAR subunits NR1 and 2A-, mGluR5-, and their respective scaffold proteins PSD95- and Homer 1-; CB1R and the neuromodulatory protein HINT1 mRNA levels were evaluated. CBD (40 mg/kg i.p.) was administered to the adolescent offspring before the cognitive tasks. Results: The present results show that prenatal THC impairs hippocampal memory functions and the underlying synaptic plasticity; CBD is able to mitigate cognitive impairment in both reinforcement- and aversion-related tasks and the neuroadaptation of hippocampal excitatory synapses and CB1R-related signaling. Discussion: While this research shows CBD potential in dampening prenatal THC-induced consequences, we point out the urgency to curb cannabis use during pregnancy in order to avoid detrimental bio-behavioral outcomes in the offspring.