Modulation of nicotine-induced attentional enhancement in rats by adrenoceptor antagonists

Rationale Understanding the neuropharmacological mechanisms mediating attentional enhancement by nicotine would help a targeted search for nicotinic compounds with retained therapeutic but reduced unwanted side-effects. Previous studies suggested that the dopamine-releasing effects of nicotine may not be of primary importance for its attention-enhancing properties.Objectives The present study examined the role of noradrenergic neurotransmission for the effects of nicotine on different response indices of an attentional paradigm.Methods The effects of systemic injections of the ₁-adrenoceptor antagonist prazosin that also displays significant affinity at _2B and _2C-adrenoceptors and the -adrenoceptor antagonist propranolol were tested in both the presence and absence of nicotine in rats trained in a version of the five-choice serial reaction time task.Results Nicotine generally enhanced the accuracy of signal detection, reduced omission errors and shortened response latencies. At the largest doses tested, both prazosin (1 mg/kg) and propranolol (10 mg/kg) impaired performance. For propranolol, these effects depended on the rate of target signal presentation. The two compounds differentially modulated the effects of nicotine. Propranolol (6 mg/kg and 10 mg/kg) but not prazosin reduced its effects on omission errors and accuracy. By contrast, prazosin (0.5 mg/kg) reversed the nicotine-induced reductions in response latency.Conclusions The data provide the first evidence that -adrenoceptors are involved in mediating the effects of nicotine on signal detection, while activation of -adrenoceptors may contribute to its effects on response speed. This is a further indication that, from among nicotines wide range of neuropharmacological effects, specific facets can be dissociated that are responsible for its attention-enhancing properties.