Effects of calcium channel blockers on pentylenetetrazol drug discrimination in rats

The effects of the dihydropyridine L-type calcium channel blockers nitrendi pine and nimodipine on the pentylenetetrazol (PTZ) drug discrimination, an operant model of anxiety, were investigated. Male Long-Evans rats were trai ned to discriminate PTZ (16 mg/kg, i.p.) from saline. Both nitrendipine (5. 0-25 mg/kg, i.p.) and nimodipine (5.0-25 mg/kg, i.p.) partially substituted for the PTZ discriminative stimulus. However, pretreatment with nitrendipi ne (25 mg/kg, i.p.) or nimodipine (25 mg/kg, i.p.) produced no change in th e PTZ dose-effect function. Rats were given a nutritionally balanced liquid diet containing 6.5% ethanol for 10 days. Rats selected the PTZ drug lever during withdrawal. Subchronic coadministration of nitrendipine (1.25-5.0 m g/kg, i.p., b.i.d.) with ethanol failed to dose-dependently reduce PTZ-leve r responding, but it did reverse withdrawal signs. Acute administration of nitrendipine (5, 10, and 20 mg/kg, i.p.) produced marked suppression of lev er responding, but it failed to significantly reduce levels of PTZ-lever re sponding. Although calcium channel blockers reduce signs of ethanol withdra wal, they also markedly reduce rates of behavior and produce no clear effec ts on anxiety-like behaviors induced by ethanol withdrawal. (C) 2001 Elsevi er Science Inc. All rights reserved.