The effects of exogenous and endogenous cannabinoids on synaptic transmission in the rat hippocampal slice
The current study investigated the effects of cannabinoids on synaptic transmission in the rat hippocampal slice. Cannabinoids have been shown to both inhibit release and inhibit uptake of GABA in the rat hippocampus. In order to identify which of these conflicting effects is functionally most significant this study has investigated the effects of the cannabinoid receptor agonist WIN55, 212-2 on paired pulse depression of population spikes recorded in the rat hippocampal slice. Manipulations which inhibit GABAergic transmission reduced, paired pulse depression whilst those that potentiate GABAergic transmission increased it, suggesting that the extent of paired pulse depression reflects the strength of GABAergic transmission. Known inhibitors of GABA uptake had no effect on paired pulse depression at 28-30°C but increased it at 35°C. AT 28-30°C WIN55, 212-2 caused a powerful decrease in paired pulse depression, an effect which is consistent with it decreasing the strength of GABAergic transmission, for example by inhibiting GABA release. However, at 35°C this effect was lost and WIN55, 212-2 caused a small potentiation of paired pulse depression, consistent with an inhibition of GABA uptake. The results show that the effects of cannabinoids on synaptic transmission in the hippocampal slice are highly temperature dependent and it is suggested that this depends on whether GABA uptake limits the action of the transmitters or not. The cannabinoid receptor agonist WIN55, 212-2 had not effect on the amplitude of the first population spike (PS1) evoked in the CA1 region of hippocampal slices prepared from young adult (4-6 weeks old) rats, despite powerfully reducing paired pulse depression. In contrast, WIN55, 212-2 caused a substantial depression of the amplitude of the first population spike (PS1) and the field excitatory postsynaptic potential (fEPSP) recorded in slices prepared from neonatal (10-13 days old) rats. This effect was stereoselective and CB1 receptor mediated. The results indicate that cannabinoid receptor mediated inhibition of excitatory synaptic transmission in the rat hippocampal slice is developmentally regulated.