TY - JOUR
T1 - Behavioral effects of benzodiazepine ligands in non-dependent, diazepam-dependent and diazepam-withdrawn baboons
AU - Sannerud, Christine A.
AU - Alien, Michael
AU - Cook, James M.
AU - Griffiths, Roland R.
N1 - Funding Information:
Wr thank S. Womack. S. Knipp. E. Koehler and S. James for their technical assistance in conductiug this study. This study was supported by National Institute on Drug Abuse Gr..tnt DA 01 147. During this project. C.A. Sannerud was supported hy National Institute on Drug Abuse National Research Service Award DA 05293.
PY - 1991/9/17
Y1 - 1991/9/17
N2 - Acute i.m. injections of benzodiazepine receptor ligands were administered to baboons before 1-h observational sessions. The agonist midazolam produced sedative effects, the antagonist flumazenil produced no behavioral effects, the inverse agonist FG7142 produced tremor and the inverse agonist 3-carboethoxy-β-carboline hydrochloride (βCCE) produced tremor, vomiting, jerks and seizures. Co-administration of these drugs (midazolam + βCCE, midazolam + flumazenil or flumazenil + βCCE) produced a mutual antagonism of these effects. Compared to the non-dependent condition, in the diazepam-dependent condition (baboons maintained on 20 mg/kg per day diazepam) and withdrawn condition (dependent baboons tested during withdrawal), midazolam produced decreased sedative effects, flumazenil produced increased effects (i.e., tremor, vomiting and jerks), and βCCE produced increased frequency of seizures. Taken together, these data suggest that (1) benzodiazepine receptor ligands lie on a continuum of behavioral activity, and (2) chronic diazepam administration alters the behavioral effects of these benzodiazepine ligands, producing a shift in the direction of the inverse agonist.
AB - Acute i.m. injections of benzodiazepine receptor ligands were administered to baboons before 1-h observational sessions. The agonist midazolam produced sedative effects, the antagonist flumazenil produced no behavioral effects, the inverse agonist FG7142 produced tremor and the inverse agonist 3-carboethoxy-β-carboline hydrochloride (βCCE) produced tremor, vomiting, jerks and seizures. Co-administration of these drugs (midazolam + βCCE, midazolam + flumazenil or flumazenil + βCCE) produced a mutual antagonism of these effects. Compared to the non-dependent condition, in the diazepam-dependent condition (baboons maintained on 20 mg/kg per day diazepam) and withdrawn condition (dependent baboons tested during withdrawal), midazolam produced decreased sedative effects, flumazenil produced increased effects (i.e., tremor, vomiting and jerks), and βCCE produced increased frequency of seizures. Taken together, these data suggest that (1) benzodiazepine receptor ligands lie on a continuum of behavioral activity, and (2) chronic diazepam administration alters the behavioral effects of these benzodiazepine ligands, producing a shift in the direction of the inverse agonist.
KW - (Baboon)
KW - 3-carboethoxy-β-carboline hydrochloride
KW - Cβ-CCE
KW - Dependence
KW - Diazepam
KW - FG7142
KW - Flumazenil
KW - GABA
KW - Midazolam
KW - γ-aminobutyric acid
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U2 - 10.1016/0014-2999(91)90290-7
DO - 10.1016/0014-2999(91)90290-7
M3 - Article
C2 - 1666365
AN - SCOPUS:0025776732
SN - 0014-2999
VL - 202
SP - 159
EP - 169
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -