title: Improvement of attentional function with antagonism of nicotinic receptors in female rats.
abstract: Nicotinic agonists have been shown in a variety of studies to improve cognitive function. Since nicotinic receptors are easily desensitized by agonists, it is not completely clear to what degree receptor desensitization or receptor activation are responsible for nicotinic agonist-induced cognitive improvement. In the current study, the effect of the neuronal nicotinic cholinergic α4β2 receptor antagonist dihydro-β-erythroidine (DHβE) and the α7 nicotinic receptor antagonist methyllycaconitine (MLA) on attentional function was determined. Adult female Sprague-Dawley rats were trained on the visual signal detection task. They were required to discriminate whether or not a light signal occurred on a trial and respond with a lever press on one side after a signal and the opposite side after the absence of a signal in order to receive a food pellet reinforcer. Acute administration of the α4β2 antagonist DHβE improved attentional function either alone or in reversing the attentional impairment caused by the NMDA glutamate antagonist dizocilpine (MK-801). Acute administration of MLA also significantly attenuated the dizocilpine-induced attentional impairment. In previous research we have shown that the α4β2 nicotinic desensitizing agent and partial agonist sazetidine-A also was effective in reversing dizocilpine-induced attentional impairments on the signal detection task and that low doses of the general nicotinic antagonist mecamylamine improved learning and memory. The current studies indicate that blockade of nicotinic receptors can effectively attenuate attentional impairments. Development of drugs that provide a net decrease in nicotinic receptor activity either through antagonism or desensitization could be worth exploring for beneficial effects for treating cognitive impairments.
authors: Department of Psychiatry and Behavioral Sciences Duke University Medical Center, Durham, NC, USA. edlevin@duke.edu
authors: Edward D
authors: ED
authors: Levin
authors: Marty
authors: M
authors: Cauley
authors: Amir H
authors: AH
authors: Rezvani
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D016291:Dizocilpine Maleate; D005260:Female; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000502:physiology*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D016291:Dizocilpine Maleate; D009538:Nicotine; D000157:Aconitine
references: Biochem Pharmacol. 2009 Oct 1;78(7):880-8
references: 19615981
references: Psychopharmacology (Berl). 2009 Jan;202(1-3):93-102
references: 18815772
references: Prog Neurobiol. 2008 Apr;84(4):329-42
references: 18242816
references: J Pharmacol Exp Ther. 2009 Feb;328(2):364-70
references: 19023041
references: Psychopharmacology (Berl). 2013 Mar;226(1):35-43
references: 23100170
references: Drugs Aging. 1997 Sep;11(3):206-28
references: 9303280
references: Psychopharmacology (Berl). 2011 Jun;215(4):621-30
references: 21274704
references: Int J Neuropsychopharmacol. 2008 Feb;11(1):63-70
references: 17295931
references: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):269-75
references: 19110025
references: Neuropharmacology. 2009 May-Jun;56(6-7):1001-9
references: 19233218
references: Psychopharmacology (Berl). 1997 Dec;134(3):230-41
references: 9438673
references: Neuroscience. 2002;109(4):757-65
references: 11927157
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):523-39
references: 16220335
references: Hum Psychopharmacol. 2009 Jun;24(4):309-17
references: 19475630
references: Neurotoxicol Teratol. 2004 Mar-Apr;26(2):239-51
references: 15019957
references: Biochem Pharmacol. 2009 Oct 1;78(7):788-94
references: 19477167
references: Psychopharmacology (Berl). 2002 Mar;160(2):140-5
references: 11875631
references: Pharmacol Biochem Behav. 2003 Aug;76(1):75-83
references: 13679219
references: Neurotoxicol Teratol. 2007 Mar-Apr;29(2):247-54
references: 17175136
references: J Physiol. 2003 Dec 15;553(Pt 3):857-71
references: 14555718
references: Eur J Pharmacol. 2000 Mar 30;393(1-3):141-6
references: 10771007
references: Cell Mol Neurobiol. 1989 Jun;9(2):141-78
references: 2663167
references: Psychopharmacology (Berl). 1998 Aug;138(3-4):231-59
references: 9725746
references: Behav Pharmacol. 1993 Apr;4(2):179-182
references: 11224184
references: Behav Neurosci. 1995 Dec;109(6):1095-105
references: 8748960
references: Pharmacol Ther. 2009 Jun;122(3):302-11
references: 19351547
references: Psychopharmacology (Berl). 1999 May;144(2):175-82
references: 10394999
references: Neurobiol Learn Mem. 2006 Jul;86(1):117-22
references: 16632386
references: J Pharmacol Exp Ther. 2011 Jan;336(1):242-53
references: 20959364
references: Psychopharmacology (Berl). 2011 Sep;217(1):75-82
references: 21432025
references: Psychopharmacology (Berl). 2012 Oct;223(3):251-8
references: 22526540
references: Eur J Pharmacol. 2003 Mar 28;465(1-2):83-90
references: 12650836
references: Biol Psychiatry. 2001 Feb 1;49(3):258-67
references: 11230877
references: Mol Pharmacol. 2008 Jun;73(6):1838-43
references: 18367540
references: Eur J Pharmacol. 2004 Feb 20;486(2):175-82
references: 14975706
references: Pharmacol Biochem Behav. 2009 Mar;92(1):141-6
references: 19041337
references: Neurotoxicol Teratol. 2008 May-Jun;30(3):167-74
references: 18299185
references: Toxicol Sci. 2005 Oct;87(2):460-8
references: 16033991