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Student Research
Symposium Oct 2006 |
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Cannabinoid
pretreatment blocks the development of tolerance to the analgesic effect of
morphine injected into the periaqueductal gray Wilson, A. &
Morgan, M. M.,
Department of
Psychology,
Washington State
University Vancouver
Cannabinoids
and opioids are known to have analgesic effects. These drugs produce analgesia,
in part, by acting on a brain structure called the periaqueductal gray (PAG).
Unfortunately, the analgesia produced by opiates such as morphine is diminished
with repeated administration because of the development of tolerance. The
objective of this study was to determine whether tolerance develops to the
analgesic effect of injecting the cannabinoid HU-210 into the PAG. Male
Spraque-Dawley rats were implanted with a guide cannula aimed at the
ventrolateral PAG. Following recovery, rats were injected twice a day for two
days with saline, morphine, HU-210, or morphine and HU-210 combined. On Day 3
all rats received cumulative doses of morphine to determine whether tolerance
had occurred. Nociception was assessed using the hot plate test. Both morphine
and HU-210 caused an increase in hot plate latency compared to saline treated
controls when injected into the PAG on Trial 1. Rats pretreated with morphine
required higher doses of morphine to produce analgesia on Day 3 than
saline-pretreated rats (i.e., the rats were tolerant). Surprisingly, rats
pretreated with HU-210 required lower doses of morphine to produce analgesia on
Day 3. Rats receiving morphine and HU-210 did not differ from saline-pretreated
controls in their response to morphine. These data demonstrate that cannabinoid
pretreatment enhances the analgesic effect of morphine and suggests that
combined opiate and cannabinoid treatment be therapeutically advantageous by
preventing the development of tolerance.
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