Impairment of hippocampal long-term potentiation following transient cerebral ischaemia in rat: effects of bifemelane, a potent inhibitor of ischaemia-induced acetylcholine release.

The present study examined the changes in the long-term potentiation (LTP) of the hippocampal Schaffer collateral/CA1 pyramidal cell system in vivo occurring after 12-min forebrain ischaemia in the rat. A population spike (PS) of CA1 pyramidal cells were recorded in 18 rats at 7 h post-ischaemia. While the threshold and amplitude of pretetanic PS were not depressed, the induction of LTP was significantly impaired following ischaemic insult (155 +/- 28% of baseline PS, mean +/- SD, n = 6, p < 0.001), as compared to sham-controls (337 +/- 84%, n = 5), without reduction of single pulse responses. Pretreatment with 4(o-benzylphenoxy)-N-methylbutylamine hydrochloride (Bifemelane; 50 mg kg-1 i.p.) slightly but significantly attenuated the impairment in LTP induction (196 +/- 23%, n = 6; p < 0.02). The findings in the present study indicate that CA1 pyramidal cells are dysfunctional in synaptic plasticity long before their death. Bifemelane has been demonstrated to inhibit acetylcholine release strongly during cerebral ischaemia but not interfere with normal cholinergic synaptic transmission. The effect of bifemelane suggests that Ach release during ischaemia is partially involved in the post-ischaemic impairment of LTP induction.