TY - JOUR
T1 - Strain differences in mice antinociception
T2 - Relationship between alprazolam and opioid receptor subtypes
AU - Pick, Chaim G.
N1 - Funding Information:
We would like to express our gratitude to Dr. G.W. Pasternak from the Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, USA, for his support of these studies. This work was supported in part by the Tel-Aviv University Foundation for Basic research.
PY - 1996/8
Y1 - 1996/8
N2 - This study was designed to investigate the antinociceptive effects of one of the most prescribed benzodiazepines (BZ) - i.e., alprazolam. Groups of CD-1, SWISS, BALB/c and C57BL mice were treated with alprazolam. Analgesia was assayed, using the radiant heat tailflick assay. Alprazolam given i.p. elicited analgesia in a dose-dependent manner only in the BALB/c mice (ED50 1.1 mg/kg). No analgesia was observed in CD-1 or C57BL mice. The sensitivity of SWISS mice was intermediate, but still very low. Intrathecally administered alprazolam elicited analgesia in BALB/c, Swiss and CD-1 mice with ED50 values of 10, 22.8 and 34.6 μg, respectively. No analgesia was observed in C57BL mice. Intracerebroventricular injections did not induce analgesia in any of the strains. In other sets of experiments with BALB/c mice, we found a supra-additivity increase in analgesia when a subthreshold dose of alprazolam was given with morphine (μ-subtype agonist). This interaction was antagonized by naloxone and less so by flumazenil. No effect was found when alprazolam was co-administered with other specific opioid agonists (δ and κ). Our results demonstrate that injections of alprazolam can produce analgesia in different genetic subjects and can modify morphine-induced antinociception. The fact that the interaction between morphine and alprazolam analgesia was sensitive to naloxone but less to flumazenil indicates that the analgesic effects of alprazolam are mediated primarily by an opioid mechanism of action but less by benzodiazepines.
AB - This study was designed to investigate the antinociceptive effects of one of the most prescribed benzodiazepines (BZ) - i.e., alprazolam. Groups of CD-1, SWISS, BALB/c and C57BL mice were treated with alprazolam. Analgesia was assayed, using the radiant heat tailflick assay. Alprazolam given i.p. elicited analgesia in a dose-dependent manner only in the BALB/c mice (ED50 1.1 mg/kg). No analgesia was observed in CD-1 or C57BL mice. The sensitivity of SWISS mice was intermediate, but still very low. Intrathecally administered alprazolam elicited analgesia in BALB/c, Swiss and CD-1 mice with ED50 values of 10, 22.8 and 34.6 μg, respectively. No analgesia was observed in C57BL mice. Intracerebroventricular injections did not induce analgesia in any of the strains. In other sets of experiments with BALB/c mice, we found a supra-additivity increase in analgesia when a subthreshold dose of alprazolam was given with morphine (μ-subtype agonist). This interaction was antagonized by naloxone and less so by flumazenil. No effect was found when alprazolam was co-administered with other specific opioid agonists (δ and κ). Our results demonstrate that injections of alprazolam can produce analgesia in different genetic subjects and can modify morphine-induced antinociception. The fact that the interaction between morphine and alprazolam analgesia was sensitive to naloxone but less to flumazenil indicates that the analgesic effects of alprazolam are mediated primarily by an opioid mechanism of action but less by benzodiazepines.
KW - Alprazolam
KW - Analgesia
KW - Flumazenil
KW - Mice
KW - Opioid receptors
KW - Strain differences
KW - Tailflick
UR - http://www.scopus.com/inward/record.url?scp=0030220627&partnerID=8YFLogxK
U2 - 10.1016/0924-977X(96)00021-1
DO - 10.1016/0924-977X(96)00021-1
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AN - SCOPUS:0030220627
SN - 0924-977X
VL - 6
SP - 201
EP - 205
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 3
ER -