TY - JOUR
T1 - Tolerance to the antinociceptive effects of ethanol during ethanol withdrawal
AU - Gatch, Michael B.
N1 - Funding Information:
This work was supported by NIAAA grants AA09567 and AA10545. I would like to acknowledge Meghan Selvig for expert technical assistance.
PY - 2006/7
Y1 - 2006/7
N2 - Prior research has indicated that tolerance develops to the antinociceptive effects of ethanol and continues even during withdrawal. Three potential pharmacological mechanisms for this tolerance are examined, using nitrendipine (L-type calcium channel blocker), theophylline (adenosine A1/A2 antagonist) and flumazenil (benzodiazepine antagonist). Rats received 10 days of exposure to an ethanol-containing liquid diet (6.5% w/v). A radiant heat tail-flick assay was used to assess hyperalgesia at 12 h after removal of the liquid diet, as well as tolerance to the effects of cumulative doses of ethanol (0.5-2 g/kg). Co-administration of flumazenil (10 mg/kg, i.p., b.i.d.), nitrendipine (5 mg/kg, i.p., b.i.d.) or theophylline (1 mg/kg, i.p., b.i.d.) with chronic ethanol prevented development of the hyperalgesia produced by ethanol withdrawal, but only theophylline reduced tolerance to the antinociceptive effects of ethanol administered during ethanol withdrawal. In contrast, when administered during ethanol withdrawal, theophylline (1-10 mg/kg) blocked the anti-hyperalgesic effects of ethanol during ethanol withdrawal, whereas nitrendipine (5-25 mg/kg) enabled ethanol to produce levels of antinociception comparable to non-dependent rats. These findings indicate that L-type calcium channels and adenosine receptors play important, but differing roles in the development of hyperalgesia during withdrawal, and to tolerance to the antinociceptive effects of ethanol.
AB - Prior research has indicated that tolerance develops to the antinociceptive effects of ethanol and continues even during withdrawal. Three potential pharmacological mechanisms for this tolerance are examined, using nitrendipine (L-type calcium channel blocker), theophylline (adenosine A1/A2 antagonist) and flumazenil (benzodiazepine antagonist). Rats received 10 days of exposure to an ethanol-containing liquid diet (6.5% w/v). A radiant heat tail-flick assay was used to assess hyperalgesia at 12 h after removal of the liquid diet, as well as tolerance to the effects of cumulative doses of ethanol (0.5-2 g/kg). Co-administration of flumazenil (10 mg/kg, i.p., b.i.d.), nitrendipine (5 mg/kg, i.p., b.i.d.) or theophylline (1 mg/kg, i.p., b.i.d.) with chronic ethanol prevented development of the hyperalgesia produced by ethanol withdrawal, but only theophylline reduced tolerance to the antinociceptive effects of ethanol administered during ethanol withdrawal. In contrast, when administered during ethanol withdrawal, theophylline (1-10 mg/kg) blocked the anti-hyperalgesic effects of ethanol during ethanol withdrawal, whereas nitrendipine (5-25 mg/kg) enabled ethanol to produce levels of antinociception comparable to non-dependent rats. These findings indicate that L-type calcium channels and adenosine receptors play important, but differing roles in the development of hyperalgesia during withdrawal, and to tolerance to the antinociceptive effects of ethanol.
KW - Adenosine receptors
KW - Ethanol withdrawal
KW - Hyperalgesia
KW - L-type calcium channels
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=33646913950&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2006.02.010
DO - 10.1016/j.pnpbp.2006.02.010
M3 - Article
C2 - 16574295
AN - SCOPUS:33646913950
SN - 0278-5846
VL - 30
SP - 946
EP - 952
JO - Progress in Neuropsychopharmacology and Biological Psychiatry
JF - Progress in Neuropsychopharmacology and Biological Psychiatry
IS - 5
ER -