Effects of calcium channel blockers on pentylenetetrazol drug discrimination in rats

Michael B. Gatch, Cleatus J. Wallis, Harbans Lal

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)141-147
Number of pages7
JournalAlcohol
Volume23
Issue number3
DOIs
StatePublished - 18 Jul 2001

Keywords

  • Anxiety
  • Calcium channel blockers
  • Drug discrimination
  • Ethanol withdrawal
  • GABA receptor
  • Nimodipine
  • Nitrendipine
  • Pentylenetetrazol

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