Different outcomes after acute and chronic treatment with nicotine in pre-pulse inhibition in Lister hooded rats.

Excessive tobacco consumption by schizophrenic patients may be a form of self-medication, and nicotine in tobacco may alleviate deficits in information processing. We tested this hypothesis by determining whether nicotine (acute/chronic) would improve information processing in the rat using pre-pulse inhibition as a model. In study 1, rats were injected with nicotine 10 min prior to placement in startle chambers (0.001-0.1 or 0.03-0.3 mg/kg, s.c.). In study 2, rats were injected with either saline or nicotine (0.4 mg/kg, s.c.) for 21 consecutive days and assessed for locomotor activity, pre-pulse inhibition and changes in [3H]nicotine binding in whole brain. Acutely, nicotine had no effect on pre-pulse inhibition. By contrast, after chronic nicotine treatment, rats demonstrated a robust deficit in pre-pulse inhibition and significant increases in locomotor activity and [3H]nicotine binding. The deficit in pre-pulse inhibition after chronic treatment with nicotine may be the result of non-specific behavioural activation due to increased mesolimbic dopamine release or, possibly, nicotine may rapidly desensitize nicotinic receptors important for normal information processing.