Effect of single and combined high and low dose verapamil and colchicine on behavior, cholinesterase and creatinine kinase in Webster albino mice.

摘要

P-glycoprotein inhibitors verapamil and colchicine interactions may affect behaviour and cholinesterase activity in mice. Groups of 7 Webster albino mice each were gavaged 50 and 70 μg/kg colchicine with or without 1.5 and 3mg/kg verapamil daily for90 days. Controls were gavaged distilled water. To evaluate behavior, 3 minute open field crossings, geotaxis, cliff, Y-maze, swim and head pocking tests were performed at days 0, 45 and 90. We determined serum acetylcholine and creatinine kinase at days45 and 90. Compared with Day 0 and water controls, by day 90, colchicine and verapamil open crossings declined ~-19-36% (P < 0.05) but combined had no effect. At Day 45, negative geotaxis was not affected but increased 61-75% by day 90. Cliff avoidanceincreased 32-77% with single drugs but only 47-52% when combined. Head pocking declined 25-63% with all treatments and 12 Y maze trials by 19-42%, but combined had no effect. We noted that 20 second swimming declined ~25% in all groups. Cholinesterase increased ~33% in mice given colchicine but declined ~15-60% with other treatments. Serum creatinine kinase declined 23-63% in mice given verapamil or combined drugs but colchicine had no effect. We found time based drug dose dependency and results suggested that higher single and combined doses had most effect on locomotor, memory and mentation.