Rationale: Nicotine can enhance attentional performance in humans, a property that may be of therapeutic utility.
Objectives: To identify brain sites mediating nicotine-induced attentional enhancement.
Methods: Nicotine (0, 1, 2, 4 and 8 microg) was injected bilaterally into the dorsal hippocampus and the prelimbic area of the prefrontal cortex, brain sites implicated in cognitive functions, of rats performing the five-choice serial reaction time task (5-CSRTT). This rodent model of attention required the detection of light stimuli presented randomly in one of five locations during 30-min sessions. Systemically administered nicotine (0.1 and 0.2 mg/kg SC) was tested alongside local injections as a positive control.
Results: Nicotine (SC) enhanced response accuracy, reduced omission errors and shortened response latency. Nicotine injected into the dorsal hippocampus had no effect on any measure of performance except a slight decrease in latency in some animals at lower doses. By contrast, local injections of nicotine into the prefrontal cortex caused a dose-related increase in accuracy, the measure most closely reflecting stimulus detection and attention. Nicotine also increased omission errors selectively in the first 10 min of sessions and slightly reduced premature responding in the intertrial interval. No effects on response latency were observed.
Conclusions: The results implicate the prefrontal cortex, but not the dorsal hippocampus, in the attention-enhancing effects of nicotine. The targeting of nicotinic receptor subtypes expressed in the prefrontal cortex may be of particular benefit for the treatment of chronic disease states characterised by attentional dysfunction.