The effects of CB1 receptor agonist HU-210 and cannabinoid CB1 receptor antagonist SR 141716A on nociception of male Wistar rats with a model of depression (bilateral olfactory bulbectomy, OBX) were studied. HU-210 (5 ñg) and SR 141716A (3 ñg) were acutely microinjected i.c.v. on the developed depression background. Nociception was examined as applied mechanical pressure on the left hind paw of the rat (analgesy-meter test, Randall & Sellitto). In the OBX rats, it was found that the pain threshold was increased. HU-210 significantly increased the pain threshold in OBX rats, i.e. decreased the pain sensitivity as compared to saline-treated OBX controls and to sham-operated controls, suggesting an implication of CB1 receptors in nociception of OBX rats. SR 141716A did not affect the nociception in OBX rats. These results suggest that stimulation of CB1 receptors in rats with a model of depression exerted antinociceptive effect.
Biochemical, physiological and behavioural changes take place during stress. Various stress models have been reported to induce analgesia. This is a phenomenon referred to as stress-induced analgesia (SIA). Two forms of SIA are commonly distinguished: an opioid-mediated and a non-opioid one.In the last decade special attention has been attributed to the endocannabinoid system (ECS) as a component of non-opioid SIA.The Tyr-MIF-1 peptides proved to have opioid-like as well as anti-opioid effects.It has been shown that the endogenous opioid and the endocannabinoid systems have been involved in stress-induced analgesia.We found no literature data about the effects of Tyr-MIF-1 neuropeptides on the endocannabinoid system after stress.The aim of the study was to investigate the effects on nociception of Tyr-MIF-1 peptides (MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1) on the endocannabinoid system after immobilization stress.Anandamide (CB1 agonist) and AM251 (CB1 antagonist) were used. Nociception was measured in male Wistar rats by paw-pressure and hot-plate tests. All drugs were injected intraperitoneally.The results showed that anandamide and AM251 were involved in the analgesic effects of Tyr-MIF-1 peptides after immobilization SIA. The effects are probably due to different interaction between Tyr-MIF-1 receptors and endocannabinoid ones and the different involvement of the opioid and the antiopioid component in immobilization stress.
Endogenous opioid peptides and nitric oxide (NO) mediate a wide variety of physiological processes including analgesia induced by stress. Various stress models have been reported to induce analgesia, a phenomenon known as stressinduced analgesia (SIA).Substitutions in the Tyr-MIF-1's molecule with amino acids L-canavanine and L-citrulline have been made.Literature data showed that L-Canavanine incorporated in MIF-1 potentates its analgesic, naloxone reversible effects.The aim of the present study was to investigate the effects of Tyr-Cav-MIF-1 and Tyr-Cit-MIF-1 on nociception after immobilization, cold and heat stress (IS, CS and HS) and the involvement of L-Arginine, L-NAME and SIN-1. All drugs were injected intraperitoneally in male Wistar rats. Nociception was measured by paw-pressure (PP) test.Our results found that both substituted peptides decreased SIA.In conclusion, we assume that there are different kinds of involvement of endogenous NO in the mechanisms of nociception of Tyr-Cit-MIF-1 and TyrCav-MIF-1 after immobilization, cold and heat stress.
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