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Sensitivity changes after morphine treatment in the mouse uterus
Abstract:
The addition of morphine to a bath containing the vas deferens from chronically morphinized mice induces a facilitatory effect on noradrenaline contractile responses. This facilitatory effect of morphine has been thought to be a dependence-like effect. In the present work the possibility that a pretreatment with morphine might induce a similar effect on the contractile responses of the mouse uterus to acetylcholine and serotonin was examined. The acute effect of morphine on the uteri of untreated mice consisted in an attenuation of the responses to both substances, whereas a long term pretreatment with morphine induced a supersensitivity state. Tolerance to the depressant action of morphine on the contractile responses induced by the stimulating compounds was also observed. Acute morphine in the uteri from morphinized mice did not induce a facilitatory effect on acetylcholine or serotonin responses. Naloxone did not modify the effects of morphine in the naive or chronically treated mice. The supersensitivity state and the intensity of tolerance were unaffected by changes in the concentration of calcium in the bath medium. Caffeine or theophylline decreased the tolerance observed in the uterus from chronically morphinized mice. The attenuation of tolerance suggests that methylxanthines induce effects opposed to those of chronic morphine in the calcium distribution within the cell.
Insights
Morphine pretreatment alters mouse uterine responses to acetylcholine and serotonin, inducing supersensitivity and tolerance. Methylxanthines like caffeine counteract these morphine-induced changes, suggesting a role in cellular calcium distribution.
Area of Science:
- Pharmacology
- Neuroscience
- Reproductive Biology
Background:
- Morphine's effect on vas deferens suggests a dependence-like facilitatory action.
- Previous research indicated morphine can induce dependence-like effects in smooth muscle preparations.
Purpose of the Study:
- To investigate if morphine pretreatment induces similar effects on mouse uterine contractile responses.
- To examine the effects of acetylcholine and serotonin on uteri from morphine-pretreated mice.
Main Methods:
- Isolated mouse uteri were used to assess contractile responses.
- Experiments involved acute morphine administration and long-term morphine pretreatment.
- Responses to acetylcholine and serotonin were measured under various conditions, including naloxone and altered calcium concentrations.
Main Results:
- Acute morphine attenuated uterine responses to acetylcholine and serotonin in naive mice.
- Long-term morphine pretreatment induced supersensitivity to these agonists and tolerance to morphine's depressant effect.
- Methylxanthines (caffeine, theophylline) reduced tolerance in uteri from chronically morphinized mice.
Conclusions:
- Long-term morphine exposure induces a supersensitivity state and tolerance in the mouse uterus, distinct from its effects on the vas deferens.
- Methylxanthines appear to oppose chronic morphine's effects, potentially by influencing intracellular calcium distribution.
- Naloxone did not alter morphine's effects, suggesting opioid receptor-independent mechanisms in this context.