Abstract
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. Microinjection of cumulative half log doses of morphine (0.32, 1, 3.2, and 10 μg/0.4 μl) produced antinociception on the hot plate test only at the two highest doses. Microinjection of quarter log doses of morphine into the PAG (1, 1.8, 3.2, 5.6, and 10 μg/0.4 μl) resulted in an ED 50 for antinociception of 1.8 μg. Systemic administration of the opioid antagonist naloxone increased the morphine ED 50 to 9.0 μg. 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 μg/0.4 μl), 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.