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Increased drinking in mutant mice with truncated M5 muscarinic receptor genes
Junichi Takeuchi1, James Fulton, Zheng-ping Jia
1Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3.
Abstract:
The rarest and least understood of the muscarinic receptors is the M5 subtype. Recombinant methods were used to create mutant mice with a deletion in the third intracellular loop of the M5 receptor gene. Salivation induced by the nonselective muscarinic agonist pilocarpine (1 mg/kg s.c.) was reduced in homozygous mutants from 15 to 60 min after injection as compared with wild-type mice. After 18-h food and water deprivation, drinking was increased in homozygous mutants, but feeding was not increased. The mutant and wild-type mice had similar responses in tests of open-field exploration, seizures induced by pilocarpine (300 mg/kg) or hypothermia induced by pilocarpine (1-3 mg/kg). These results indicate that M5 muscarinic receptors are important for fluid intake and suggest that M5 receptors are involved in slow secretory processes.
Insights
The M5 muscarinic receptor is crucial for regulating fluid intake and influences slow secretory processes. Mutant mice lacking a functional M5 receptor showed altered drinking behaviors and reduced salivation.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The M5 muscarinic receptor is the rarest and least understood subtype.
- Muscarinic receptors play vital roles in physiological processes, including secretion and fluid balance.
Purpose of the Study:
- To investigate the physiological role of the M5 muscarinic receptor.
- To characterize the function of M5 receptors in fluid intake and secretion using a genetically modified mouse model.
Main Methods:
- Generation of mutant mice with a deletion in the third intracellular loop of the M5 receptor gene using recombinant methods.
- Assessment of salivation, drinking, and feeding behaviors in response to pilocarpine administration.
- Evaluation of behavioral responses including open-field exploration, pilocarpine-induced seizures, and hypothermia.
Main Results:
- Homozygous mutant mice exhibited reduced salivation compared to wild-type mice following pilocarpine injection.
- Mutant mice showed increased drinking behavior after food and water deprivation, but feeding remained unchanged.
- No significant differences were observed in open-field exploration, pilocarpine-induced seizures, or hypothermia between mutant and wild-type mice.
Conclusions:
- M5 muscarinic receptors are essential for regulating fluid intake.
- The M5 receptor subtype appears to be involved in modulating slow secretory processes, such as salivation.