title: Selective nicotinic receptor antagonists: effects on attention and nicotine-induced attentional enhancement.
abstract: BACKGROUND
  The question of the subtype(s) of the nicotinic acetylcholine receptor (nAChR) mediating the attention-enhancing effects of nicotine is still unsettled. While early studies pointed towards subtypes other than the homomeric α7 nAChR, pro-cognitive effects of α7 nAChR agonists have since been demonstrated.
  
  
  OBJECTIVE
  This study tested whether the performance-enhancing effects of nicotine in a rodent model of attention could be reversed by the α4β2, α4β4, α3β2, and α2β2 nAChR antagonist dihydro-β-erythroidine (DHβE), or the α7 antagonist methyllycaconitine (MLA).
  
  
  METHODS
  In repeated tests, 12 rats trained to perform the 5-choice serial reaction time task were systemically injected with nicotine or vehicle in the presence of increasing doses of DHβE or MLA.
  
  
  RESULTS
  DHβE did not antagonize the attention-enhancing effects of nicotine reflected by measures of accuracy and omission errors, suggesting that its previously reported antagonism of nicotine effects on latency and anticipatory responses specifically reflected the stimulant effects of nicotine. MLA dose-dependently reversed the reduction in omission errors by nicotine. In the absence of nicotine, low doses of MLA (0.4 and 1.3 mg/kg) not previously tested on attention improved response accuracy, resulting in an inverted U-shape dose-response function.
  
  
  CONCLUSIONS
  nAChR subtypes involved in the performance-enhancing effects of nicotine appear to vary depending on the function assessed. Our findings suggest a greater involvement of α7 nAChRs in the effects of nicotine on attention than first suggested by preclinical studies, with different optimal receptor tones for aspects of stimulus detection and response readiness to task stimuli.
authors: University of Maryland School of Medicine, Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD 21228, USA. bhahn@mprc.umaryland.edu
authors: Britta
authors: B
authors: Hahn
authors: Mohammed
authors: M
authors: Shoaib
authors: Ian P
authors: IP
authors: Stolerman
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000157:Aconitine