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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
On the mechanism of tolerance to morphine-induced Straub tail reaction in mice
M R Zarrindast1, K Alaei-Nia, M Shafizadeh
1Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Abstract:
The effect of 5-HT and opioid receptor antagonists on morphine-induced Straub tail was studied in mice. Straub tail behavior was induced by subcutaneous administration of different doses (20, 30, and 40 mg/kg) of morphine hydrochloride to mice. The effect of morphine was dose-dependent. Maximum response was obtained with 40 mg/kg of the drug. The response induced by morphine (20 and 40 mg/kg) was decreased by different doses of intraperitoneal injection of naloxone (1 and 2 mg/kg) or methysergide, mianserin, and ritanserin (1 and 2 mg/kg). The effect of morphine (40 mg/kg) was also reduced by intracerebroventricular injection of naloxone (0.4-0.8 microg/animal) or mianserin (2 and 4 microg/animal). Different groups of mice received one daily dose (50 mg/kg sc) of morphine sulfate for 3 days to develop tolerance to morphine. The Straub tail reaction induced by morphine hydrochloride (40 mg/kg) was tested on the fourth day. Naloxone injection (1 and 2 mg/kg ip) on Day 3 (1 h after morphine sulfate injection) or on Day 4 (1 h before test dose of morphine hydrochloride), decreased tolerance induced to morphine. Methysergide, mianserin, or ritanserin (intraperitoneal) on Days 2 and 3 (1 h after morphine sulfate injection) or on Day 4 (1 h before test dose of morphine hydrochloride), also decreased tolerance induced to morphine. Intracerebroventricular injection of either naloxone or mianserin also reduced tolerance to morphine. It is concluded that 5-HT(2) and opioid receptor mechanisms are involved in morphine-induced Straub tail reaction and tolerance induced to morphine also may be mediated through these receptors.
Insights
Opioid and serotonin antagonists reduce morphine-induced Straub tail and tolerance in mice. These findings suggest 5-HT(2) and opioid receptors are key mechanisms in morphine
Area of Science:
- Neuropharmacology
- Pain Research
Background:
- Morphine is a widely used analgesic.
- The Straub tail phenomenon is a characteristic behavioral response to morphine administration in rodents.
- Understanding the neurobiological underpinnings of morphine's effects is crucial for optimizing its therapeutic use and managing side effects.
Purpose of the Study:
- To investigate the involvement of serotonin (5-HT) and opioid receptors in morphine-induced Straub tail behavior in mice.
- To examine the role of these receptors in the development of tolerance to morphine.
Main Methods:
- Straub tail behavior was induced in mice using various doses of morphine hydrochloride.
- The effects of opioid receptor antagonists (naloxone) and serotonin receptor antagonists (methysergide, mianserin, ritanserin) were assessed following systemic and central administration.
- Morphine tolerance was induced by repeated daily administration of morphine sulfate, and the influence of antagonists on this tolerance was evaluated.
Main Results:
- Morphine-induced Straub tail was dose-dependent, with the maximum response at 40 mg/kg.
- Both naloxone and serotonin antagonists significantly reduced morphine-induced Straub tail.
- Administration of these antagonists also attenuated the development of morphine tolerance, both when given during tolerance induction and before testing.
Conclusions:
- Serotonin 5-HT(2) and opioid receptor systems play a significant role in mediating the Straub tail response to morphine.
- The development of tolerance to morphine may also involve these serotonergic and opioid receptor pathways.
