Hippocampal TRPV1 channels in the modulation of contextual fear conditioning
Psychiatric disorders have been linked to impairments in fear memory circuitry. Thus, pharmacological approaches that impair aversive memories have been investigated as new treatments. The TRPV1 channel modulates biological processes related to memory consolidation and retrieval. However, TRPV1 seems involved in memories generated by high intense conditioning. Anandamide (AEA), the main endocannabinoid, is an agonist of both, TRPV1 channels and CB1 receptors which are colocalized in several brain structures. Remarkably, AEA has twenty-times more affinity for CB1 than for TRPV1, which may be involved in the intensity-dependent recruitment of this channel. In order to evaluate the role of intensity of the conditioning in the recruitment of TRPV1, the animals were submitted to the contextual fear conditioning (CFC) and conditioned with low, moderate or high intensity. Before the retrieval a TRPV1 blocker was administered into the dorsal hippocampus (dHPC). The levels of AEA were quantified by Mass Spectrometry. The RNA levels of Arc, Zif and Trkb, involved in memory and plasticity, were quantified by PCR. Our results showed that TRPV1 blockers impair the retrieval of memory in animals conditioned with moderate and high intensity but not low ones. As revealed by Mass Spectrometry, this different recruitment among intensities seems to be associated with the levels of AEA released. Moreover, the impairment in freezing induced by blocking TRPV1 was prevented by a subeffective dose of the cannabinoid receptor CB1 antagonist which suggest that TRPV1 blockers act increasing AEA availability in the synaptic cleft to act through CB1 receptors. Despite blocking TRPV1 channels impairs freezing in moderate and high intensities, it increases the RNA levels of Arc, Zif and Trkb only in animals conditioned with the moderate intensity. In accordance, the treatment impairs retrieval in both intensities but only in the moderate intensity is able to prevent the reinstatement. Summarizing, our results suggested that intensity of the conditioning modulates AEA levels which in turns determines if TRPV1 will be recruited at the retrieval and which molecular pathways will be engaged due to TRPV1 blocking.