Neuroplastic alterations in cannabinoid receptors type 1 (CB1) in animal models of epileptic seizures

Currently, there is an urgent need to better comprehend neuroplastic alterations in cannabinoid receptors type 1 (CB1) and to understand the biological meaning of these alterations in epileptic disorders. The present study reviewed neuroplastic changes in CB1 distribution, expression, and functionality in animal models of epileptic seizures. Neuroplastic alterations in CB1 were consistently observed in chemical, genetic, electrical, and febrile seizure models. Most studies assessed changes in hippocampal and cortical CB1, while thalamic, hypothalamic, and brainstem nuclei were rarely investigated. Additionally, the relationship between CB1 alteration and the control of brain excitability through modulation of specific neuronal networks, such as striatonigral, nigrotectal and thalamocortical pathways, and inhibitory projections to hippocampal pyramidal neurons, were all presented and discussed in the present review. Neuroplastic alterations in CB1 detected in animal models of epilepsy may reflect two different scenarios: (1) endogenous adaptations aimed to control neuronal hyperexcitability in epilepsy or (2) pathological alterations that facilitate neuronal hyperexcitability. Additionally, a better comprehension of neuroplastic and functional alterations in CB1 can improve pharmacological therapies for epilepsies and their comorbidities.