Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Sep 2006
Antinociceptive tolerance revealed by cumulative intracranial microinjections of morphine into the periaqueductal gray in the rat.
The periaqueductal gray (PAG) appears to play a key role in morphine antinociception and tolerance. The objective of this manuscript is to develop a cumulative dose microinjection procedure so the hypothesized role of the PAG in morphine antinociceptive tolerance can be assessed using dose-response analysis. Rats were implanted with a guide cannula into the ventrolateral PAG. ⋯ Repeated microinjections of saline into the PAG had no effect on nociception. Pretreatment with twice daily injections of morphine, either systemically (5 mg/kg, s.c.) or into the PAG (5 micro g/0.4 micro l), for 2 days produced a two-fold increase in the ED(50) for morphine antinociception. These data validate the use of an intracranial cumulative dose procedure to assess morphine potency and demonstrate that microinjection of morphine into the PAG is sufficient to produce tolerance.
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Pharmacol. Biochem. Behav. · Sep 2006
Gabapentin enhances the analgesic response to morphine in acute model of pain in male rats.
Whenever opioids as drug of choice result in inadequate analgesia, the combinational therapy would be the solution. In this study the co-administration of gabapentin with morphine is evaluated in acute model of pain. Therefore the antinociceptive effect of gabapentin (30 or 90 mg/kg, s.c.) and morphine (0.5, 1 or 3 mg/kg, s.c.) alone or in combination were measured by tail-flick test in intact adult male rats. ⋯ The co-administration of gabapentin with analgesic doses of 1 and 3 mg/kg morphine had also increased significantly AUC. Therefore gabapentin enhanced the antinociceptive effect of both analgesic and subanalgesic doses of morphine in a dose dependent manner. In conclusion co-administration of gabapentin with low doses of morphine produced therapeutic analgesia which could have important clinical application.