Aβ25-35-induced depression of long-term potentiation in area CA1 in vivo and in vitro is attenuated by verapamil

The effect of intracerebroventricular (icv) injection of Abeta(25-35) 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 Abeta(25-35) (10 nmol in 5 mul, 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 Abeta(25-35) (500 nmol), verapamil (20 muM), or diltiazem (50 muM). Combined application of Abeta(25-35) 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 Abeta(25-35) 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 Abeta 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.