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Comparison of the development of tolerance following chronic in‐vivo exposure to opioid (morphine) versus cannabinoid receptor agonists (WIN‐55,212‐2)
Author(s) -
Maguma Hercules T,
Taylor David A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.712.5
Subject(s) - cannabinoid , damgo , opioid , morphine , pharmacology , in vivo , cannabinoid receptor , drug tolerance , agonist , chemistry , cross tolerance , medicine , opioid receptor , receptor , biology , microbiology and biotechnology
Few studies have determined if the heterologous tolerance that develops in the guinea pig longitudinal muscle‐myenteric plexus (LM/MP) following in‐vivo opioid treatment extends to cannabinoids; nor, have studies compared the nature of tolerance that develops after chronic in‐vivo exposure to opioids with that after cannabinoids. To induce tolerance, morphine was injected twice daily for 7 days and WIN‐55,212‐2 once daily for 5 days. The LM/MP was used to assess the degree and character of tolerance by comparing the ability of opioid, adenosine and cannabinoid agonists to inhibit neurogenic contractions. Animals exposed to morphine showed tolerance to all inhibitory agonists (ratios of IC 50 values of 4.8 [DAMGO], 3.6 [2‐chloroadenosine] and 4.9 [WIN‐55,212‐2]). In contrast, WIN‐55,212‐2 exposure resulted in reduced maximum responses and subsensitivity to WIN‐55,212‐2 only (IC 50 ratio of 10.5) with no change in sensitivity all other agonists including nicotine. Thus, the heterologous tolerance in the LM/MP after in‐vivo opioid treatment extends to cannabinoid agonists and may involve non‐receptor coupled changes. In contrast, tolerance that develops after in‐vivo WIN‐55,212‐2 exposure is associated with reduced sensitivity and maximum responses specific to cannabinoid agonists that suggests tolerance following chronic in‐vivo cannabinoid exposure may involve receptor‐dependent modifications.