Effect of nicotine, lobeline, and mecamylamine on sensory gating in the rat.
In normal subjects, if an acoustic startle stimulus is immediately preceded by a small brief change in background noise intensity, the magnitude of the subsequent startle response is decreased. This prepulse inhibition (PPI) of an acoustic startle response has been shown to be associated with sensorimotor gating. PPI is disrupted in schizophrenic patients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 mumol/kg IP) (equivalent to 0.03, 0.1, and 0.3 mg/kg base) and the nicotinic cholinergic receptor (nAChR) channel blocker, mecamylamine (5.0 and 50 mumol/kg IP) (equivalent to 1.0 and 10.0 mg/kg) on PPI of the acoustic startle response in the rat. Nicotine increased the PPI at the lowest prepulse signal levels but not at the stronger levels. Mecamylamine was without effect at 5.0 mumol/kg, but the 50 mumol/kg dose decreased the inhibition at both weak and strong prepulse (PP) levels. Mecamylamine (5.0 mumol/kg) pretreatment did not block the (-)-nicotine-induced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mumol/kg IP) (equivalent to 0.071, 0.23, 0.71, and 2.3 mg/kg) was without effect. These results are consistent with a mecamylamine-insensitive effect of nicotine to improve gating in normal rats. The nAChR subtype involved in producing nicotine's increase of PPI needs further investigation.
Curzon
P
P
Neuroscience Department, Abbott Laboratories, Abbott Park, IL 60064-3500.
Kim
D J
DJ
Decker
M W
MW
D000161:Acoustic Stimulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*
D008464:Mecamylamine; D009538:Nicotine; D008120:Lobeline