Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-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 non-psychoactive 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.

Department of Biological Chemical and Pharmaceutical Sciences and Technologies and ATEN Center University of Palermo Palermo Italy

Department of Biomedicine Neuroscience and Advanced Diagnostics University of Palermo Palermo Italy

Department of Health Promotion Mother and Child Care Internal Medicine and Medical Specialties of Excellence G D'Alessandro University of Palermo Palermo Italy

Fondazione Policlinico Universitario A Gemelli IRCSS Rome Italy

Forensic Laboratory of Biologically Active Compounds Department of Chemistry of Natural Compounds University of Chemistry and Technology Prague Czechia

Pharmacology Section Department of Healthcare Surveillance and Bioethics Università Cattolica del Sacro Cuore Rome Italy

Psychedelics Research Centre National Institute of Mental Health Prague Czechia

Citace poskytuje Crossref.org