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Acute administration of a cannabinoid CB1 receptor antagonist impairs stress-induced antinociception in fish
Carla Patrícia Bejo Wolkers1, Augusto Barbosa Junior1, Leda Menescal-de-Oliveira1
1School of Medicine of Ribeirão Preto, São Paulo University, Physiology Department, Bandeirantes Avenue 3900, Zip Code 14049-900, Ribeirão Preto, SP, Brazil.
Abstract:
This study evaluated the influence of the pre-treatment with AM251 (a cannabinoid type I receptor (CB1) selective antagonist) on the stress-induced antinociception promoted by restraint in the fish Leporinus macrocephalus. The application of 3 and 5 min of restraint stress promoted an inhibition of the behavioural response to the subcutaneous injection of 3% formaldehyde (increase in locomotor activity), suggesting the activation of an antinociceptive system. The acute intraperitoneal administration of AM251 (3 mg·kg(-1)) impaired this antinociceptive response induced by 3 and 5 min of restraint stress. The fish treated with AM251 before the application of restraint stress presented an increase in locomotor activity after the subcutaneous injection of formaldehyde, similar to fish not exposed to restraint, suggesting that the stress-induced antinociception promoted by restraint in fish is probably mediated by cannabinoid CB1 receptors. The results presented in this paper suggest the participation of the endocannabinoid system in nociception modulation in fish, supporting the hypothesis that an endogenous antinociceptive system activated by restraint stress is present in fish and that the modulation of antinociception by the CB1 receptor is evolutionary well-conserved across vertebrates.
Insights
Restraint stress activates an internal pain-relief system in fish, likely involving cannabinoid type I (CB1) receptors. Blocking CB1 receptors with AM251 disrupts this stress-induced antinociception, indicating conserved pain modulation across vertebrates.
Area of Science:
- Neuroscience
- Animal Behavior
- Pharmacology
Background:
- The endocannabinoid system plays a role in pain modulation in vertebrates.
- Stress can activate endogenous antinociceptive (pain-relieving) mechanisms.
Purpose of the Study:
- To investigate the role of cannabinoid type I (CB1) receptors in stress-induced antinociception in the fish Leporinus macrocephalus.
- To determine if restraint stress activates an endogenous antinociceptive system in fish.
Main Methods:
- Fish (Leporinus macrocephalus) were subjected to restraint stress (3 or 5 minutes).
- Locomotor activity was measured following formaldehyde injection to assess nociception.
- AM251, a CB1 receptor antagonist, was administered intraperitoneally before stress exposure.
Main Results:
- Restraint stress significantly reduced the behavioral response to formaldehyde injection, indicating antinociception.
- Pre-treatment with AM251 blocked the antinociceptive effect of restraint stress.
- Fish treated with AM251 showed increased locomotor activity after formaldehyde injection, similar to unstressed fish.
Conclusions:
- Stress-induced antinociception in fish appears to be mediated by cannabinoid CB1 receptors.
- The endocannabinoid system is involved in nociception modulation in fish.
- CB1 receptor modulation of antinociception is evolutionarily conserved in vertebrates.
