TY - JOUR
T1 - Effects of GABAA compounds on mCPP drug discrimination in rats
AU - Gatch, Michael B.
AU - Jung, Marianna E.
AU - Wallis, Cleatus J.
AU - Lal, Harbans
N1 - Funding Information:
This work was supported by NIAAA grants AA09567 and AA10545. We would like to acknowledge Meghan Selvig for expert technical assistance.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002/10/18
Y1 - 2002/10/18
N2 - Male Long-Evans rats were trained to discriminate mCPP (1.4 mg/kg, i.p.) from saline, using a two-lever, food-reinforced operant task. The GABAA antagonist, bicuculline (0.16-0.64 mg/kg), partially substituted for mCPP, whereas the benzodiazepine antagonist, flumazenil (1-10 mg/kg), and the benzodiazepine inverse agonist, Ro 15-4513 (0.25-2.5 mg/kg), failed to substitute for mCPP. Bicuculline produced no change in response rate, whereas Ro 15-4513 dose-dependently decreased responding. Flumazenil produced a small increase in response rates. Flumazenil (10 mg/kg), Ro 15-4513 (1.25 mg/kg), and the benzodiazepine agonists alprazolam (0.64 mg/kg) and diazepam (5 mg/kg) full agonist all failed to block the mCPP discriminative stimulus. When given in combination with mCPP, Ro 15-4513 and alprazolam both produced lower response rates than did mCPP alone, whereas flumazenil and diazepam did not significantly alter response rates. These findings provide evidence that GABAA antagonists modulate the discriminative stimulus effects of mCPP, but that these effects are not mediated by activity at the benzodiazepine site.
AB - Male Long-Evans rats were trained to discriminate mCPP (1.4 mg/kg, i.p.) from saline, using a two-lever, food-reinforced operant task. The GABAA antagonist, bicuculline (0.16-0.64 mg/kg), partially substituted for mCPP, whereas the benzodiazepine antagonist, flumazenil (1-10 mg/kg), and the benzodiazepine inverse agonist, Ro 15-4513 (0.25-2.5 mg/kg), failed to substitute for mCPP. Bicuculline produced no change in response rate, whereas Ro 15-4513 dose-dependently decreased responding. Flumazenil produced a small increase in response rates. Flumazenil (10 mg/kg), Ro 15-4513 (1.25 mg/kg), and the benzodiazepine agonists alprazolam (0.64 mg/kg) and diazepam (5 mg/kg) full agonist all failed to block the mCPP discriminative stimulus. When given in combination with mCPP, Ro 15-4513 and alprazolam both produced lower response rates than did mCPP alone, whereas flumazenil and diazepam did not significantly alter response rates. These findings provide evidence that GABAA antagonists modulate the discriminative stimulus effects of mCPP, but that these effects are not mediated by activity at the benzodiazepine site.
KW - 5-HT (5-hydroxytryptamine, serotonin)
KW - Drug discrimination
KW - GABA receptor
KW - Rat
KW - mCPP (1-(3-chlorophenyl)-piperazine)
UR - http://www.scopus.com/inward/record.url?scp=0037131613&partnerID=8YFLogxK
U2 - 10.1016/S0024-3205(02)02111-2
DO - 10.1016/S0024-3205(02)02111-2
M3 - Article
C2 - 12354584
AN - SCOPUS:0037131613
SN - 0024-3205
VL - 71
SP - 2657
EP - 2665
JO - Life Sciences
JF - Life Sciences
IS - 22
ER -