BACKGROUND: Neuronal nicotinic receptor systems have been shown to play key roles in cognition. Nicotine and nicotinic analogs improve attention and nicotinic antagonists impair it. This study was conducted to investigate the role of α4β2 nicotinic receptors in sustained attention using a novel selective α4β2 nicotinic receptor ligand, sazetidine-A. METHODS: Female rats were trained to perform the signal detection task to a stable baseline of accuracy. The rats were injected with saline, sazetidine-A (0.01, 0.03, and 0.1 mg/kg), dizocilpine (0.05 mg/kg), or their combination; or, in another experiment, the rats were injected with the same doses of sazetidine-A, scopolamine (0.02 mg/kg), or their combination. RESULTS: Percent hit and percent correct rejection showed that dizocilpine caused significant (p < 0.025) impairments in performance, which were significantly reversed by each of the sazetidine-A doses. Response omissions were significantly (p < 0.05) increased by dizocilpine, and this was also significantly reversed by each of the sazetidine-A doses. None of the sazetidine-A doses had significant effects on hit, correct rejection, or response omissions when given alone. Scopolamine also caused significant (p < 0.0005) impairments in percent hit and percent correct rejection and increased response omissions, which were significantly attenuated by all the sazetidine-A doses for percent hit and response omissions and by the highest dose of sazetidine-A for percent correct rejection. Both scopolamine and dizocilpine significantly (p < 0.0005) increased response latency, an effect which was significantly attenuated by sazetidine-A coadministration. CONCLUSIONS: These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Very low doses of sazetidine-A or drugs with a similar profile may provide therapeutic benefit for reversing attentional impairment in patients suffering from mental disorders and/or cognitive impairment.
BACKGROUND: Neuronal nicotinic receptor systems have been shown to play key roles in cognition. Nicotine and nicotinic analogs improve attention and nicotinic antagonists impair it. This study was conducted to investigate the role of α4β2 nicotinic receptors in sustained attention using a novel selective α4β2 nicotinic receptor ligand, sazetidine-A. METHODS: Female rats were trained to perform the signal detection task to a stable baseline of accuracy. The rats were injected with saline, sazetidine-A (0.01, 0.03, and 0.1 mg/kg), dizocilpine (0.05 mg/kg), or their combination; or, in another experiment, the rats were injected with the same doses of sazetidine-A, scopolamine (0.02 mg/kg), or their combination. RESULTS: Percent hit and percent correct rejection showed that dizocilpine caused significant (p < 0.025) impairments in performance, which were significantly reversed by each of the sazetidine-A doses. Response omissions were significantly (p < 0.05) increased by dizocilpine, and this was also significantly reversed by each of the sazetidine-A doses. None of the sazetidine-A doses had significant effects on hit, correct rejection, or response omissions when given alone. Scopolamine also caused significant (p < 0.0005) impairments in percent hit and percent correct rejection and increased response omissions, which were significantly attenuated by all the sazetidine-A doses for percent hit and response omissions and by the highest dose of sazetidine-A for percent correct rejection. Both scopolamine and dizocilpine significantly (p < 0.0005) increased response latency, an effect which was significantly attenuated by sazetidine-A coadministration. CONCLUSIONS: These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Very low doses of sazetidine-A or drugs with a similar profile may provide therapeutic benefit for reversing attentional impairment in patients suffering from mental disorders and/or cognitive impairment.
Authors: S E Molchan; A M Mellow; B A Lawlor; H J Weingartner; R M Cohen; M R Cohen; T Sunderland Journal: Psychopharmacology (Berl) Date: 1990 Impact factor: 4.530
Authors: E D Levin; C K Conners; D Silva; S C Hinton; W H Meck; J March; J E Rose Journal: Psychopharmacology (Berl) Date: 1998-11 Impact factor: 4.530
Authors: Simon Sydserff; E J Sutton; Dekun Song; Michael C Quirk; Carla Maciag; Chaoying Li; Gerald Jonak; David Gurley; John C Gordon; Edward P Christian; James J Doherty; Tom Hudzik; Edwin Johnson; Ladislav Mrzljak; Tim Piser; Gennady N Smagin; Yi Wang; Dan Widzowski; Jeffrey S Smith Journal: Biochem Pharmacol Date: 2009-07-16 Impact factor: 5.858
Authors: Amir H Rezvani; Olga Timofeeva; Hannah G Sexton; Damien DeCuir; Yingxian Xiao; Christopher J Gordon; Kenneth J Kellar; Edward D Levin Journal: Eur J Pharmacol Date: 2012-02-24 Impact factor: 4.432
Authors: Alvin V Terry; Jerry J Buccafusco; R Foster Schade; Leah Vandenhuerk; Patrick M Callahan; Wayne D Beck; Elizabeth J Hutchings; James M Chapman; Pei Li; Michael G Bartlett Journal: Biochem Pharmacol Date: 2012-01-08 Impact factor: 5.858