TY - JOUR
T1 - Comparison of the discriminative stimulus effects of midazolam after intracranial and peripheral administration in the rat
AU - Sannerud, Christine A.
AU - Ator, Nancy A.
AU - Griffiths, Roland R.
N1 - Funding Information:
We thank Dr. Nick E. Goeders for his help in initiating this line of research, E. Kinch and T. McCassell for their technical assistance in conducting this study, Dr. Charles Schindler for his help with the statistical analyses, and A.J.G. Alastra for his help in the data analyses and figure preparation. This study was supported by National Institute on Drug Abuse Grant DA 04133.
PY - 1991
Y1 - 1991
N2 - Rats were trained in a two-lever drug discrimination paradigm to discriminate midazolam (0.32 mg/kg, i.p. or 1.0 mg/kg, i.p.) from the no-drug condition. After completion of i.p. and s.c. midazolam generalization gradients (0.032-1.0 mg/kg), rats were surgically implanted with unilateral cannulae into the lateral ventricles. Intracerebroventricular (i.c.v.) doses of 1.1-44.2 μg midazolam were delivered to unrestrained rats. Midazolam produced dose-dependent increases in drug-appropriate responding by all three routes of administration, but was 2.4- to 4.3-fold more potent when given i.c.v. than when given s.c. or i.p. Midazolam, over the dose range tested, did not produce substantial decreases in response rate by any route of administration. The discriminative-stimulus effect of i.c.v. midazolam was blocked by peripherally administered flumazenil, and such antagonism was surmounted by a 2- to 5-fold increase in the i.c.v. midazolam dose. Taken together, these data suggest that the discriminative-stimulus effects of midazolam are mediated via central benzodiazepine (BZ) receptors.
AB - Rats were trained in a two-lever drug discrimination paradigm to discriminate midazolam (0.32 mg/kg, i.p. or 1.0 mg/kg, i.p.) from the no-drug condition. After completion of i.p. and s.c. midazolam generalization gradients (0.032-1.0 mg/kg), rats were surgically implanted with unilateral cannulae into the lateral ventricles. Intracerebroventricular (i.c.v.) doses of 1.1-44.2 μg midazolam were delivered to unrestrained rats. Midazolam produced dose-dependent increases in drug-appropriate responding by all three routes of administration, but was 2.4- to 4.3-fold more potent when given i.c.v. than when given s.c. or i.p. Midazolam, over the dose range tested, did not produce substantial decreases in response rate by any route of administration. The discriminative-stimulus effect of i.c.v. midazolam was blocked by peripherally administered flumazenil, and such antagonism was surmounted by a 2- to 5-fold increase in the i.c.v. midazolam dose. Taken together, these data suggest that the discriminative-stimulus effects of midazolam are mediated via central benzodiazepine (BZ) receptors.
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U2 - 10.1016/0024-3205(91)90012-Z
DO - 10.1016/0024-3205(91)90012-Z
M3 - Article
C2 - 1649362
AN - SCOPUS:0025850559
SN - 0024-3205
VL - 49
SP - 261
EP - 268
JO - Life Sciences
JF - Life Sciences
IS - 4
ER -