Orexin and cannabinoid systems modulate long-term potentiation of the hippocampus CA1 area in anesthetized rats

Abstract

Objectives: Long-term potentiation (LTP) is a kind of synaptic plasticity and has a key role in learning and memory. Endocannabinoids and orexins are the endogenous systems that can modulate synaptic plasticity. Given that new studies have shown an interaction between cannabinoid and orexin systems in the brain, we decided to examine this interaction between the two systems on LTP induction in rat's hippocampus.

Materials and methods: Twenty-eight male Wistar rats were used for evaluating the effects of co-administrating of cannabinoid-1 receptor (CB1R) antagonist (AM251) and orexin-2 receptor (OX2R) antagonist (TCS OX2 29) on the induction of LTP in the Schaffer collateral-CA1 synapses of rat hippocampus. The drugs were microinjected into the CA1 area of rat hippocampus 30 min before inducing of LTP.

Results: Results showed that sole administration of the antagonists inhibited LTP, with respect to the control group. Also, co-administrating of them reduced LTP as compared to the control group, but not significantly more than that when the antagonists were solely microinjected into the CA1. Nonetheless, the inhibitory effect of concurrent administration of the antagonists on LTP lasted until the end of the recording.

Conclusion: These results propose that endogenous cannabinoids and orexins play a role in the expression of LTP, at least by CA1-CB1Rs and CA1-OX2Rs, respectively. Finally, there is no interaction between CB1R and OX2R on the induction of LTP in the Schaffer collateral-CA1 synapses; therefore, these two systems possibly act through common signaling pathways in the hippocampus's CA1 region.

Keywords: AM251; Cannabinoid receptors; Hippocampus; Long-term potentiation; Orexin receptors; TCS OX2 29.

Figure 1

Schematic diagram of fEPSP

Figure 2

A schematic representation of the Schaffer collateral pathway (left) and CA1 (right) adapted from Paxinos and Watson, showing the site of the stimulating electrode (S) in the Schaffer collateral pathway and recording electrode (R) and injection needle (I) in CA1 region

Figure 3

Time-dependent changes in CA1 responses to Schaffer collateral stimulation following an HFS

Figure 4

Time-dependent changes in CA1 responses to Schaffer collateral stimulation following an HFS

Figure 5

An original trace of the induced field potentials in the CA1 area at the pre-HFS (baseline) and post-HFS time-points