Acute Δ9‐tetrahydrocannabinol prompts rapid changes in cannabinoid CB₁ receptor immunolabeling and subcellular structure in CA1 hippocampus of young adult male mice

Abstract

The use and abuse of cannabis can be associated with significant pathophysiology, however, it remains unclear whether (1) acute administration of Δ‐9‐tetrahydrocannabinol (THC) during early adulthood alters the cannabinoid type 1 (CB1) receptor localization and expression in cells of the brain, and (2) THC produces structural brain changes. Here we use electron microscopy and a highly sensitive pre‐embedding immunogold method to examine CB1 receptors in the hippocampus cornu ammonis subfield 1 (CA1) 30 min after male mice were exposed to a single THC injection (5 mg/kg). The findings show that acute exposure to THC can significantly decrease the percentage of CB1 receptor immunopositive terminals making symmetric synapses, mitochondria, and astrocytes. The percentage of CB1 receptor‐labeled terminals forming asymmetric synapses was unaffected. Lastly, CB1 receptor expression was significantly lower at terminals of symmetric and asymmetric synapses as well as in mitochondria. Structurally, CA1 dendrites were significantly larger, and contained more spines and mitochondria following acute THC administration. The area of the dendritic spines, synaptic terminals, mitochondria, and astrocytes decreased significantly following acute THC exposure. Altogether, these results indicate that even a single THC exposure can have a significant impact on CB1 receptor expression, and can alter CA1 ultrastructure, within 30 min of drug exposure. These changes may contribute to the behavioral alterations experienced by young individuals shortly after cannabis intoxication.

Axonal CB1 receptors mediate inhibitory bouton formation via cAMP increase

“…4A, B). In addition, there was significant CB1 background staining, presumably reflecting CB1 receptors in pyramidal cells and glia cells (Bonilla-Del Río et al, 2021). CB1R-axons had a higher bouton density and higher bouton turnover compared to CB1R+ axons (Fig.…”

“…CB1 receptors are G-protein coupled receptors and are widely abundant in the brain. They are expressed in both excitatory and inhibitory neurons, as well as in glia cells (Bonilla-Del Río et al, 2021;Hebert-Chatelain et al, 2016;Maroso et al, 2016;Navarrete et al, 2014). Perhaps the most prominent CB1 expression is in a subset of inhibitory axons in the dendritic layer of the hippocampal CA1 area (Bonilla-Del Río et al, 2021;Dudok et al, 2015).…”

“…They are expressed in both excitatory and inhibitory neurons, as well as in glia cells (Bonilla-Del Río et al, 2021;Hebert-Chatelain et al, 2016;Maroso et al, 2016;Navarrete et al, 2014). Perhaps the most prominent CB1 expression is in a subset of inhibitory axons in the dendritic layer of the hippocampal CA1 area (Bonilla-Del Río et al, 2021;Dudok et al, 2015). Axonal CB1 signaling plays an important role during axon guidance (Argaw et al, 2011;Berghuis et al, 2007;Njoo et al, 2015;Roland et al, 2014), but axonal CB1 receptor expression remains high during adulthood.…”

Acute Delta 9‐tetrahydrocannabinol administration differentially alters the hippocampal opioid system in adult female and male rats

“…Recent studies in the CA1 region of male mice have demonstrated that acute THC can increase the percentage of CB1 terminals forming symmetric synapses and increase the area of pyramidal cell dendrites but decrease the size of dendritic spines (Bonilla‐Del Río et al., 2020).…”

“…Recent studies in the CA1 region of male mice have demonstrated that acute THC can increase the percentage of CB1 terminals forming symmetric synapses and increase the area of pyramidal cell dendrites but decrease the size of dendritic spines (Bonilla-Del Río et al, 2020). However, it is unknown whether acute THC induces changes in the hippocampal opioid system and whether these changes are sex-specific.…”