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Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration
Published on: February 10, 2012
Modulation of nicotine-induced attentional enhancement in rats by adrenoceptor antagonists
1Neuroimaging Research Branch, NIH/NIDA/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. bhahn@intra.nida.nih.gov
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 alpha(1)-adrenoceptor antagonist prazosin that also displays significant affinity at alpha(2B) and alpha(2C)-adrenoceptors and the beta-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 beta-adrenoceptors are involved in mediating the effects of nicotine on signal detection, while activation of alpha-adrenoceptors may contribute to its effects on response speed. This is a further indication that, from among nicotine's wide range of neuropharmacological effects, specific facets can be dissociated that are responsible for its attention-enhancing properties.
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