Cannabigerol does not affect contextual fear memory in mice but modulates nociception in a sex-dependent manner

Conditioned fear is a response to contexts or cues previously paired with aversive stimuli. Substances from the herb Cannabis sativa (phytocannabinoids), such as cannabidiol (CBD), prevent fear responses and hold potential as new treatments for certain psychiatric disorders, such as post-traumatic stress disorder. The phytocannabinoid cannabigerol (CBG), similarly to CBD, lacks psychotomimetic effects and targets multiple receptors involved in fear-related pathways. This study tested the hypothesis that CBG inhibits memory acquisition, consolidation, and retrieval/expression in contextual fear conditioning (CFC) in both male and female C57BL/6 J mice. We also characterized CBG for its activity upon nociceptive and motor responses. Animals were submitted to CFC protocols and CBG (3, 10, or 30 mg/kg) was administered at different timepoints to assess its effect in each memory phase. CBG failed to significantly change the acquisition, consolidation or retrieval/expression of contextual fear memories. Because CFC relies on nociceptive stimuli (shocks), we also evaluated the effects of CBG on the tail-flick test. A biphasic antinociceptive effect occurred 30 min after drug administration in female animals, in which the doses of 3 mg/kg and 30 mg/kg, respectively, increased and reduced the latency for withdrawal response. Finally, no motor impairment was observed in the rotarod test either 30 or 120 min after CBG administration. In summary, CBG (3-30 mg/kg) failed to interfere with CFC in male and female mice, although it induced a biphasic effect on nociceptive response. Future experiments should investigate the role of this substance in different protocols, memory phases, and aversive memory models.