Aβ25–35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil

Abstract

The effect of intracerebroventricular (icv) injection of Aβ25–35 and/or intraperitoneal (ip) application of the L-type calcium channel (VDCC) blockers verapamil or diltiazem were examined in vivo. To by-pass possible systemic actions of these agents, their effects on long-term potentiation (LTP) in the CA1 region of the in vitro hippocampal slice preparation were also examined. Application of Aβ25–35 (10 nmol in 5 μl, icv) significantly impaired LTP in vivo, as did IP injection of verapamil (1 or 10 mg/kg) or diltiazem (1 or 10 mg/kg). In the in vitro slice preparation, LTP was also depressed by prior application of Aβ25–35 (500 nmol), verapamil (20 μM), or diltiazem (50 μM). Combined application of Aβ25–35 and verapamil in either the in vivo or in vitro preparation resulted in a significant reversal of the LTP depression observed in the presence of either agent alone. However, co-application of diltiazem and Aβ25–35 failed to attenuate the depression of LTP observed in the presence of either agent alone in vivo or in vitro. Since LTP is a cellular correlate of memory and Aβ is known to be involved in Alzheimer's disease (AD), these results indicate that verapamil, a phenylalkylamine, may be useful in the treatment of cognitive deficits associated with AD.