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Cross-tolerance between morphine and clonidine: a study on motility in rats
M Bartoletti1, M Gaiardi, C Gubellini
1Institute of Pharmacology, University of Bologna, Italy.
Neuropharmacology
|November 1, 1989
Summary
Clonidine suppressed motility in naive rats, but showed cross-tolerance in morphine-dependent rats. Post-dependent rats did not exhibit altered responses to clonidine, suggesting distinct mechanisms.
Area of Science:
- Pharmacology
- Neuroscience
- Behavioral Science
Background:
- Morphine dependence involves complex physiological adaptations.
- Clonidine, an alpha-2 adrenergic agonist, has shown varied effects on behavior.
- Understanding drug interactions and tolerance is crucial in addiction research.
Purpose of the Study:
- To investigate the effects of clonidine on locomotor activity in rats with varying degrees of morphine dependence.
- To determine if tolerance to morphine confers cross-tolerance to clonidine.
- To explore the relationship between morphine and clonidine's effects on motility.
Main Methods:
- Assessing locomotor activity in naive, morphine-dependent, and post-dependent rats following clonidine administration.
- Administering varying doses of clonidine (30-100 micrograms/kg) to different rat groups.
- Establishing morphine dependence through daily intraperitoneal injections (20 mg/kg for 26 days).
Main Results:
- Clonidine dose-dependently reduced motility in naive rats.
- Morphine-dependent rats exhibited hyperactivity at low clonidine doses and reduced motility only at the highest dose.
- Post-dependent rats showed no significant difference in clonidine's effects compared to controls.
Conclusions:
- Tolerance to morphine appears to confer cross-tolerance to clonidine's suppressive effects on motility.
- The findings suggest overlapping, yet distinct, neurobiological pathways for morphine and clonidine.
- Clonidine's effects are modulated by the state of morphine dependence and withdrawal.