Effects of calcium channel blockers on pentylenetetrazol drug discrimination in rats.
The effects of the dihydropyridine L-type calcium channel blockers nitrendipine and nimodipine on the pentylenetetrazol (PTZ) drug discrimination, an operant model of anxiety, were investigated. Male Long-Evans rats were trained 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 nitrendipine (25 mg/kg, i.p.) or nimodipine (25 mg/kg, i.p.) produced no change in the 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 mg/kg, i.p., b.i.d.) with ethanol failed to dose-dependently reduce PTZ-lever responding, but it did reverse withdrawal signs. Acute administration of nitrendipine (5, 10, and 20 mg/kg, i.p.) produced marked suppression of lever responding, but it failed to significantly reduce levels of PTZ-lever responding. Although calcium channel blockers reduce signs of ethanol withdrawal, they also markedly reduce rates of behavior and produce no clear effects on anxiety-like behaviors induced by ethanol withdrawal.
Gatch
M B
MB
Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. mgatch@hsc.unt.edu
Wallis
C J
CJ
Lal
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004032:Diet; D004192:Discrimination, Psychological / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage; D007700:Kinetics; D008297:Male; D009553:Nimodipine / Q000008:administration & dosage / Q000494:pharmacology; D009568:Nitrendipine / Q000008:administration & dosage / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy
D002121:Calcium Channel Blockers; D000431:Ethanol; D009553:Nimodipine; D009568:Nitrendipine; D010433:Pentylenetetrazole