Effects of anticholinergic drugs selective for muscarinic receptor subtypes on prepulse inhibition in mice.
The effects of anticholinergic drugs selective for muscarinic receptor subtypes on prepulse inhibition of acoustic startle response were determined in mice. The prepulse inhibition is associated with sensorimotor information processing in the brain. The anticholinergic agent scopolamine (0.3 mg/kg, s.c.) significantly attenuated prepulse inhibition, while the drug (1-10 mg/kg, s.c.) had no effects on startle amplitude as an indicator of startle response. The muscarinic M(1) receptor antagonist pirenzepine (0.1-10 microg/mouse, i.c.v.) and the muscarinic M(2) receptor antagonist AF-DX116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) (0.1-10 microg/mouse, i.c.v.) had no effects on prepulse inhibition or startle amplitude. The muscarinic M(3) receptor antagonist 4-DAMP (1,1-dimethyl-4-diphenylacetoxy-piperidinium iodide) (30 microg/mouse, i.c.v.) and the muscarinic M(4) receptor antagonist tropicamide (0.1 microg/mouse, i.c.v.) significantly attenuated prepulse inhibition, while tropicamide (0.01 microg/mouse, i.c.v.) but not 4-DAMP (10 and 30 microg/mouse, i.c.v.) produced a significant increase in startle amplitude. These results suggest that the blockade of muscarinic M(3) and M(4) receptors leads to the disruption of prepulse inhibition.
Ukai
Makoto
M
Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya 468-8503, Japan. ukai@ccmfs.meijo-u.ac.jp
Okuda
Ami
A
Mamiya
Takayoshi
T
D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000502:physiology; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000502:physiology; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D014331:Tropicamide / Q000494:pharmacology
D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D012601:Scopolamine; D014331:Tropicamide; C048593:otenzepad