The interactive role of CB1 and GABA(B) receptors in hippocampal synaptic plasticity in rats

Long-term potentiation (LTP) of synaptic transmission is a cellular process underlying learning and memory. Cannabinoids are known to be powerful modulators of this kind of synaptic plasticity. Changes in GABAergic inhibition have also been shown to affect synaptic plasticity in the hippocampus. GABA receptor type B (GABA(B)) and cannabinoid receptor type 1 (CBI) exhibit overlapping anatomical localization in some brain areas including the hippocampus. CB1 and GABA(B) are also localized to the same cells and share a common signaling pathway in some brain areas. In this study, we examined the hippocampal effects of co-administrating AM251 and CGP55845, which are CB1 and GABA(B) antagonists, respectively, on LTP induction in the dentate gyrus (DG) of rats. LTP in the hippocampal area was induced by high-frequency stimulation (HFS) of the perforant path. Our results showed that HFS coupled with administration of the CB1 antagonist increased both the population spike (PS) amplitude and field excitatory post-synaptic potential (fEPSP). Conversely, the GABA(B) antagonist decreased these parameters along with decreased LTP induction. We also demonstrated that the co-administration of CB1 and GABA(B) antagonists had different effects on the PS amplitude and fEPSP slope. It is likely that GABA(B) receptor antagonists modulate cannabinoid outputs that cause a decrease in synaptic plastisity, while in the simultaneous consumption of two antagonists, CBI antagonists can alter the release of GABA which in turn results in enhancement of LTP induction. These findings suggest that there are functional interactions between the CB1 and GABA(B) receptor in the hippocampus. (C) 2015 Elsevier Inc. All rights reserved.