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Modification of morphine-induced analgesia and toxicity by pertussis toxin
K Lutfy1, S C Chang, J Candido
1College of Pharmacy and Allied Health Professions, St. John's University, Queens, NY 11439.
Abstract:
The present study evaluates the effect of pertussis toxin (PTX) on morphine-induced analgesia and lethality. Mice were injected with 0.2 microgram PTX intracerebroventricularly (i.c.v.) and 0.2 micrograms PTX intrathecally (i.t.) or saline. Mice were tested for morphine-induced analgesia (tail flick) and lethality 16 days later; mice were also examined for pentobarbital-induced mortality. Morphine analgesic potency was decreased by approximately 4-fold in PTX-treated mice compared to controls. Conversely, the lethal potency of morphine was increased by 10-fold in PTX-treated mice compared to controls. PTX treatment did not alter the lethal potency of pentobarbital. Morphine-induced analgesia and lethality were dose-dependently antagonized by naloxone in both PTX and saline-treated groups. The results of this study suggest that morphine analgesia is mediated through PTX-sensitive G proteins. On the other hand, morphine-induced lethality appears to be limited by PTX-sensitive factor(s) since PTX treatment enhanced morphine's lethal potency. The increase in lethal potency of morphine may be due to unmasking of an excitatory opioid receptor mediated effect by PTX.
Insights
Pertussis toxin (PTX) significantly reduces morphine
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Background:
- Pertussis toxin (PTX) is known to affect G protein signaling pathways.
- Opioid analgesia and lethality are complex physiological responses.
- The role of PTX-sensitive factors in opioid effects requires further investigation.
Purpose of the Study:
- To investigate the impact of pertussis toxin (PTX) on morphine-induced analgesia and lethality in mice.
- To determine if PTX alters the dose-response relationship for morphine's effects.
- To elucidate the involvement of PTX-sensitive pathways in opioid pharmacology.
Main Methods:
- Mice received intracerebroventricular or intrathecal injections of PTX or saline.
- Following a 16-day period, mice were assessed for morphine-induced analgesia (tail flick test) and lethality.
- Pentobarbital-induced mortality was also evaluated to control for general toxicity.
Main Results:
- PTX treatment decreased morphine analgesic potency approximately 4-fold.
- Conversely, PTX treatment increased morphine lethal potency by approximately 10-fold.
- PTX did not affect the lethal potency of pentobarbital, indicating specificity.
Conclusions:
- Morphine analgesia appears to be mediated by PTX-sensitive G proteins.
- Morphine-induced lethality may be regulated by PTX-sensitive factors, as PTX enhances its lethal effects.
- PTX might unmask excitatory opioid receptor-mediated effects contributing to increased morphine lethality.