CORRELATION BETWEEN CANNABINOID MEDIATED EFFECTS ON PAIRED-PULSE DEPRESSION AND INDUCTION OF LONG-TERM POTENTIATION IN THE RAT HIPPOCAMPAL SLICE

Cannabinoids cause an increase in synaptic transmission via gamma-amin obutyric acid (GABA) receptors and this may be the mechanism by which activation of CBI receptors blocks the induction of long-term potentia tion (LTP). To test this hypothesis, we used paired pulse depression ( PPD) of CA1 population spike responses recorded in the rat hippocampal slice as an index of GABA-ergic feedback inhibition, to establish whe ther the effects of a stereoselective CB1 receptor agonist on GABA-erg ic transmission and LTP were correlated. The active isomer, WIN55212-2 , blocked the induction of LTP and suppressed PPD over the concentrati on range-250 nM-5 mu M, whereas the inactive isomer, WIN55212-3, was i nactive at 5 mu M. The effects of 5 mu M WIN55212-2 on both LTP and PP D were completely blocked by the CB1 receptor antagonist SR141716A (5 mu M). The results show that the effects are correlated in that both s uppression of PPD and blockade of induction of LTP are probably mediat ed by CB1 receptors. However, the suppression in PPD suggests that WIN 55212-2 caused a decrease in GABA-ergic feedback transmission which wo uld be expected to facilitate, rather than block, the induction of LTP . We therefore conclude that the blockade of LTP by cannabinoids is no t via upregulation of GABA-ergic synaptic transmission. (C) 1998 Elsev ier Science Ltd. All rights reserved.