A{beta}25-35-Induced Depression of Long-Term Potentiation in Area CA1 In Vivo and In Vitro Is Attenuated by Verapamil

• Published in: Journal of neurophysiology Vol. 89; no. 6; p. 3061
• Main Authors: Freir, D. B, Costello, D. A, Herron, C. E
• Format: Journal Article
• Language: English
• Published: Am Phys Soc 01.06.2003
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00992.2002

Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Earlsfort Terrace, Dublin 2, Ireland Submitted 31 October 2002; accepted in final form 22 January 2003 The effect of intracerebroventricular (icv) injection of A 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 A 25–35 (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 A 25–35 (500 nmol), verapamil (20 µM), or diltiazem (50 µM). Combined application of A 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 A 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 A 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. Address for reprint requests: C. E.Herron, Dept. of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, Univ. College Dublin, Earlsfort Terrace, Dublin 2, Ireland (E-mail: Caroline.Herron{at}ucd.ie ).