PMID- 1649362
OWN - NLM
STAT- MEDLINE
DCOM- 19910820
LR  - 20190701
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 49
IP  - 4
DP  - 1991
TI  - Comparison of the discriminative stimulus effects of midazolam after intracranial 
      and peripheral administration in the rat.
PG  - 261-8
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 micrograms 
      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.
FAU - Sannerud, C A
AU  - Sannerud CA
AD  - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School 
      of Medicine, Baltimore, MD 21205.
FAU - Ator, N A
AU  - Ator NA
FAU - Griffiths, R R
AU  - Griffiths RR
LA  - eng
GR  - DA 04133/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Receptors, GABA-A)
RN  - 40P7XK9392 (Flumazenil)
RN  - R60L0SM5BC (Midazolam)
SB  - IM
MH  - Animals
MH  - *Discrimination Learning
MH  - Flumazenil/pharmacology
MH  - Injections, Intraperitoneal
MH  - Injections, Intraventricular
MH  - Injections, Subcutaneous
MH  - Male
MH  - Midazolam/*administration & dosage/antagonists & inhibitors/pharmacology
MH  - Rats
MH  - Receptors, GABA-A/metabolism
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 0024-3205(91)90012-Z [pii]
AID - 10.1016/0024-3205(91)90012-z [doi]
PST - ppublish
SO  - Life Sci. 1991;49(4):261-8. doi: 10.1016/0024-3205(91)90012-z.