Increased drinking in mutant mice with truncated M5 muscarinic receptor genes.

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.