Behavioral and electrophysiological studies of chronic oral administration of L-type calcium channel blocker verapamil on learning and memory in rats

It has been shown that L-type voltage dependent calcium channels (VDCCs) have important role in learning and memory. In vivo and in vitro electrophysiological recordings of hippocampal neurons have demonstrated their involvement in long-term potentiation (LTP), which considers being one possible cellular mechanism underlying learning and memory. The long-term effect of VDCCs of hippocampal dentate gyrus (DG) so far on synaptic plasticity has not received much attention. In this study, the effect of chronic (60 days) oral administration of L-type calcium channel blocker verapamil on learning and memory and synaptic plasticity of hippocampal dentate gyrus in rats has been investigated. L-type calcium channel antagonist, verapamil chronically and orally at different doses (10, 20 and 50 mg/kg) was used to investigate learning and memory by passive avoidance learning. LTP in perforant-DG synapses was assessed (by either 200 or 400 Hz tetanization) in order to investigate long-term effect of verapamil on synaptic plasticity. In this case, field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. Our behavioral study has shown that chronic oral treatment of verapamil has no effect on learning whereas verapamil (50 mg/kg) decreased memory retrieval. Verapamil (20 and 50 mg/kg) inhibited EPSP-LTP induction at 400 Hz but not at 200 Hz tetanization. Furthermore, only verapamil (50 mg/kg) decreased PS-LTP with respect to control group. These data suggest that 400 Hz LTP is required for activation of L-type VDCCs and it seems that verapamil is more effective on L-type calcium channels of DG dendrites than their soma.