STRAIN DIFFERENCES IN MICE ANTINOCICEPTION - RELATIONSHIP BETWEEN ALPRAZOLAM AND OPIOID RECEPTOR SUBTYPES

This study was designed to investigate the antinociceptive effects of one of the most prescribed benzodiazepines (BZ) - i.e., alprazolam. Gr oups of CD-1, SWISS, BALB/c and C57BL mice were treated with alprazola m. Analgesia was assayed, using the radiant heat tailflick assay. Alpr azolam given i.p. elicited analgesia in a dose-dependent manner only i n the BALB/c mice (ED(50) 1.1 mg/kg). No analgesia was observed in CD- I or C57BL mice. The sensitivity of SWISS mice was intermediate, but s till very low. Intrathecally administered alprazolam elicited analgesi a in BALB/c, Swiss and CD-1 mice with ED(50) values of 10, 22.8 and 34 .6 mu g, respectively. No analgesia was observed in C57BL mice. Intrac erebroventricular injections did not induce analgesia in any of the st rains. In other sets of experiments with BALB/c mice, we found a supra -additivity increase in analgesia when a subthreshold dose of alprazol am was given with morphine (mu-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 agonis ts (delta 6 and kappa). Our results demonstrate that injections of alp razolam can produce analgesia in different genetic subjects and can mo dify morphine-induced antinociception. The fact that the interaction b etween 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 b enzodiazepines.