TY - JOUR
T1 - Effects of calcium channel blockers on pentylenetetrazol drug discrimination in rats
AU - Gatch, Michael B.
AU - Wallis, Cleatus J.
AU - Lal, Harbans
PY - 2001/7/18
Y1 - 2001/7/18
N2 - 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.
AB - 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.
KW - Anxiety
KW - Calcium channel blockers
KW - Drug discrimination
KW - Ethanol withdrawal
KW - GABA receptor
KW - Nimodipine
KW - Nitrendipine
KW - Pentylenetetrazol
UR - http://www.scopus.com/inward/record.url?scp=0034934978&partnerID=8YFLogxK
U2 - 10.1016/S0741-8329(01)00123-9
DO - 10.1016/S0741-8329(01)00123-9
M3 - Article
C2 - 11435024
AN - SCOPUS:0034934978
VL - 23
SP - 141
EP - 147
JO - Alcohol
JF - Alcohol
SN - 0741-8329
IS - 3
ER -