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


OBJECTIVE
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.
Hahn
Britta
B
Neuroimaging Research Branch, NIH/NIDA/IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. bhahn@intra.nida.nih.gov
Stolerman
Ian P
IP
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009538:Nicotine; D011433:Propranolol; D011224:Prazosin