EFFECT OF NICOTINE, LOBELINE, AND MECAMYLAMINE ON SENSORY GATING IN THE RAT

In normal subjects, if an acoustic startle stimulus is immediately pre ceded by a small brief change in background noise intensity, the magni tude of the subsequent startle response is decreased. This prepulse in hibition (PPI) of an acoustic startle response has been shown to be as sociated with sensorimotor gating. PPI is disrupted in schizophrenic p atients and has been linked to attentional disorders characteristic of this disease. We tested the effects of (-)-nicotine, (0.19, 0.62, and 1.9 pmol/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 mu mol/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. M ecamylamine was without effect at 5.0 mu mol/kg, but the 50 pmol/kg do se decreased the inhibition at both weak and strong prepulse (PP) leve ls. Mecamylamine (5.0 mu mol/kg) pretreatment did not block the (-)-ni cotineinduced increase in PPI. Lobeline (0.19, 0.62, 1.9, and 6.2 mu m ol/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 invest igation.