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Oxotremorine-tolerance: muscarinic blockade or homeostatic adaptation?
Abstract:
Tremorine pretreatment of mice induces tolerance to some effects of oxotremorine. In the state of tolerance even the highest doses of oxotremorine did not cause antinociception, this blockade being insurmountable. Oxotremorine decreased motility and amphetamine hypermotility, and both effects were diminished by tremorine pretreatment. Amphetamine hypermotility increased in the tolerance state. The increase of cerebral acetylcholine level due to oxotremorine was diminished by tremorine pretreatment. It is suggested that a special blockade of cerebral muscarinic receptors might play a role in the tolerance phenomenon, moreover it is possible that some excitation develops in the CNS. A homeostatic adaptation may be involved a role in this kind of tolerance.
Insights
Tremorine pretreatment induces tolerance to oxotremorine
Area of Science:
- Neuropharmacology
- Drug Tolerance
- Central Nervous System (CNS) Adaptations
Background:
- Tremorine pretreatment in mice can lead to tolerance to certain oxotremorine effects.
- Oxotremorine's impact on antinociception, motility, and amphetamine-induced hypermotility is a key area of study.
Purpose of the Study:
- To investigate the mechanisms behind tremorine-induced tolerance to oxotremorine.
- To examine the effects of this tolerance on various physiological responses and neurotransmitter levels.
Main Methods:
- Mice were pretreated with tremorine to induce tolerance.
- Subsequent administration of oxotremorine was used to assess effects on antinociception, motility, and cerebral acetylcholine levels.
- Amphetamine-induced hypermotility was also measured in tolerant and non-tolerant states.
Main Results:
- Tolerance to oxotremorine's antinociceptive effects was insurmountable.
- Oxotremorine-induced decrease in motility and amphetamine hypermotility were diminished by tremorine pretreatment.
- The increase in cerebral acetylcholine levels by oxotremorine was reduced in tolerant mice, with increased amphetamine hypermotility observed.
Conclusions:
- A blockade of cerebral muscarinic receptors likely contributes to tremorine-induced tolerance.
- Evidence suggests potential central nervous system excitation and homeostatic adaptation in this tolerance phenomenon.