The effect of cannabinoids on synaptic transmission in the rat hippocampal slice
Cannabinoids inhibit long term potentiation (LTP) in the hippocampus in a stereospecific, and therefore receptor mediated way, although the mechanism by which this occurs is not known. Cannabinoids also modulate the GABAergic system although conflicting reports describe both up and down regulation. This study was designed to investigate the effects of cannabinoids on GABAergic transmission using paired pulse depression (PPD) as an index of the strength of inhibition. The effect of cannabinoids on LTP was also investigated to assess whether the cannabinoid effects on the two forms of plasticity were correlated. Throughout the study population spike recordings from rat hippocampal slices were used. The cannabinoid agonist WIN55,212-2 had no effect on low frequency transmission, but reduced PPD and blocked the induction of LTP. These effects were dose-dependent, stereoselective and were reversed by the CB1 receptor antagonist SR141716A. Contrary to expectations this reduction in PPD was not mimicked by the metabotropic glutamate receptor agonists L-AP4 and DCG-IV. Such a reduction in PPD by cannabinoids indicates a reduction in GABAergic transmission and is therefore unlikely to be the mechanism by which cannabinoids block LTP.