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
N1 - Funding Information:
The authors would like to acknowledge the technical assistance of Ms. Meghan Selvig and Ms. Susan Barefield, RALAT. Dr. Wallis is now with Information Technology Services, University of North Texas Health Science Center. This investigation was supported by grants AA10545 and AA09567 from the National Institute on Alcohol Abuse and Alcoholism.
PY - 2001
Y1 - 2001
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
SN - 0741-8329
VL - 23
SP - 141
EP - 147
JO - Alcohol
JF - Alcohol
IS - 3
ER -