Cannabinoid receptor mediated inhibition of excitatory synaptic transmission in the rat hippocampal slice is developmentally regulated.

The cannabinoid (CB) receptor agonist WIN55,212-2 (500 nM) had no effect on the first of a pair of population spikes 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 single population spike (reduced to 43% control) and the field EPSP (reduced to 72% of control) recorded in slices prepared from neonatal (10 - 13 days old) rats. This effect was stereoselective and blocked by the CB(1) receptor antagonist AM281 (500 nM). The results indicate that activation of CB(1) receptors inhibits excitatory synaptic transmission in neonatal, but not adult rat hippocampus. This developmental regulation of CB(1) receptor mediated control of excitatory transmission may help explain some, but not all, of the previous discrepancies in the literature.