PMID- 11981598
OWN - NLM
STAT- MEDLINE
DCOM- 20020716
LR  - 20191210
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 161
IP  - 2
DP  - 2002 May
TI  - Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in 
      the discriminative stimulus effects of triazolam in squirrel monkeys.
PG  - 180-8
AB  - RATIONALE: Conventional benzodiazepines (BZs), clinically used for treatment of 
      anxiety and insomnia, bind to GABA(A) receptors containing alpha(1), alpha(2), 
      alpha(3), or alpha(5) subunits. The role of these different GABA(A) receptor 
      subtypes in mediating the subjective effects of BZs remains largely unknown. 
      OBJECTIVE: The purpose of the present study was to evaluate the role of GABA(A) 
      receptors containing the alpha(1) or alpha(5) subunits in the discriminative 
      stimulus (DS) effects of the conventional BZ agonist triazolam. METHODS: Squirrel 
      monkeys were trained to discriminate triazolam (0.03 mg/kg, i.v.) from vehicle 
      under a fixed-ratio 10 schedule of food reinforcement. RESULTS: The 
      GABA(A)/alpha(1)-preferring agonists zolpidem and zaleplon engendered responses 
      predominantly on the triazolam lever (73-80% drug-lever responding), and the 
      GABA(A)/alpha(1) partial agonist CL 218,872 engendered an average maximum of less 
      than 50% triazolam-lever responding. The GABA(A)/alpha(1)-preferring antagonists 
      beta-carboline-3-carboxylate-t-butyl ester (betaCCT) and 
      3-(propyloxy)-beta-carboline (3-PBC) blocked the DS effects of triazolam and 
      zolpidem in a surmountable manner. Schild analyses for betaCCT and 3-PBC in 
      combination with triazolam and zolpidem suggest that the interactions between 
      these compounds were competitive in nature and mediated by a common population of 
      receptors, presumably GABA(A)/alpha(1) receptors. In contrast, the 
      GABA(A)/alpha(5)-preferring agonist QH-ii-66 did not engender triazolam-lever 
      responding regardless of dose and did not alter the DS effects of triazolam when 
      administered in combination. CONCLUSIONS: The results are consistent with 
      GABA(A)/alpha(1) receptor involvement in mediating the DS effects of triazolam. 
      In contrast, binding to GABA(A)/alpha(5) receptors may not play a critical role 
      in mediating triazolam's DS effects.
FAU - Lelas, Snjezana
AU  - Lelas S
AD  - Harvard Medical School, New England Regional Primate Research Center, 
      Southborough, MA 01772-9102, USA.
FAU - Rowlett, James K
AU  - Rowlett JK
FAU - Spealman, Roger D
AU  - Spealman RD
FAU - Cook, James M
AU  - Cook JM
FAU - Ma, Chunrong
AU  - Ma C
FAU - Li, Xiaoyan
AU  - Li X
FAU - Yin, Wenyuan
AU  - Yin W
LA  - eng
GR  - DA11792/DA/NIDA NIH HHS/United States
GR  - DA13591/DA/NIDA NIH HHS/United States
GR  - MH46851/MH/NIMH NIH HHS/United States
GR  - RR00168/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020313
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (3-propoxy-beta-carboline)
RN  - 0 (Anti-Anxiety Agents)
RN  - 0 (Carbolines)
RN  - 0 (GABA Agonists)
RN  - 0 (GABA Antagonists)
RN  - 0 (GABA Modulators)
RN  - 0 (GABA-A Receptor Agonists)
RN  - 0 (QH-II-66)
RN  - 0 (Receptors, GABA-A)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 1HM943223R (Triazolam)
RN  - 93835-05-3 (tert-butyl beta-carboline-3-carboxylate)
SB  - IM
MH  - Animals
MH  - Anti-Anxiety Agents/*pharmacology
MH  - Benzodiazepines/pharmacology
MH  - Carbolines/pharmacology
MH  - Discrimination, Psychological/*drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - GABA Agonists/pharmacology
MH  - GABA Antagonists/pharmacology
MH  - GABA Modulators/pharmacology
MH  - GABA-A Receptor Agonists
MH  - Male
MH  - Models, Statistical
MH  - Reaction Time/drug effects/physiology
MH  - Receptors, GABA-A/*physiology
MH  - Saimiri
MH  - Triazolam/*pharmacology
EDAT- 2002/05/01 10:00
MHDA- 2002/07/18 10:01
CRDT- 2002/05/01 10:00
PHST- 2001/09/01 00:00 [received]
PHST- 2002/01/26 00:00 [accepted]
PHST- 2002/05/01 10:00 [pubmed]
PHST- 2002/07/18 10:01 [medline]
PHST- 2002/05/01 10:00 [entrez]
AID - 10.1007/s00213-002-1037-y [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2002 May;161(2):180-8. doi: 10.1007/s00213-002-1037-y. 
      Epub 2002 Mar 13.