Assessing effects of tamoxifen on tolerance, dependence, and glutamate and glutamine levels in frontal cortex and hippocampus in chronic morphine treatment

This study, therefore, evaluated effects of tamoxifen on development of analgesic tolerance and dependence, and brain glutamate and glutamine levels in chronic morphine administration. Mice implanted with placebo or morphine pellets were injected with tamoxifen (0.6-2mg/kg) or vehicle twice daily for 3 days. Nociceptive response was evaluated in the hot plate and tail immersion tests, 4, 48 and 72h post-implant, and following a challenge dose of morphine (10mg/kg). Withdrawal signs were determined after naloxone (1mg/kg) administration. Morphine increased nociceptive threshold which declined over time. At 72h, acute morphine elicited tolerance to the analgesic effect in the hot plate test in vehicle or tamoxifen administered animals. In the tail immersion test, however, tolerance to morphine analgesia was observed in tamoxifen, but not vehicle, co-administration. Tamoxifen did not reduce withdrawal signs. In contrast to previous reports, glutamate and glutamine levels in the hippocampus and frontal cortex did not change in the morphine-vehicle group. Confirming previous findings, tamoxifen (2mg/kg) decreased glutamate and glutamine concentrations in the hippocampus in animals with placebo pellets. Both doses of tamoxifen significantly changed glutamate and/or glutamine concentrations in both regions in morphine pellet implanted animals. These results suggest that tamoxifen has no effect on dependence but may facilitate tolerance development to the antinociception, possibly me...
Source: Brain Research - Category: Neurology Authors: Source Type: research