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Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention.
Biol Psychol 2011; 88(1):83-93BP

Abstract

Given the cognitive-promoting properties of the nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled nicotine in schizophrenia has been interpreted as an attempt to self-correct cognitive deficits, which have been particularly pronounced in the attentional domain. As glutamatergic abnormalities have been implicated in these attentional deficiencies, this study attempted to shed light on the separate and interactive roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the modulation of attention by investigating, in healthy volunteers, the separate and combined effects of nicotine and the NMDAR antagonist ketamine on neural and behavioural responses in a sustained attention task. In a randomized, double-blind, placebo controlled study, performance and the P300 event-related brain potential (ERP) in a visual information processing (RVIP) task were examined in 20 smokers and 20 non-smokers (both male and female). Assessment involved intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo gum. Nicotine-enhanced attentional processing was most evident in nonsmokers, with both performance accuracy and P300 amplitude measures. Ketamine's detrimental effects on these behavioural and electrophysiologic measures were negatively moderated by acute nicotine, the synergistic effects being expressed differently in smokers and nonsmokers. These findings support the view that acute alterations and individual differences in nAChR function can moderate even subtle glutamatergic-driven cognitive deficiencies in schizophrenia and can be important therapeutic targets for treating cognitive impairments in schizophrenia.

Authors+Show Affiliations

University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. Verner.Knott@rohcg.on.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21742012

Citation

Knott, Verner J., et al. "Separate and Combined Effects of Low Dose Ketamine and Nicotine On Behavioural and Neural Correlates of Sustained Attention." Biological Psychology, vol. 88, no. 1, 2011, pp. 83-93.
Knott VJ, Millar AM, McIntosh JF, et al. Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention. Biol Psychol. 2011;88(1):83-93.
Knott, V. J., Millar, A. M., McIntosh, J. F., Shah, D. K., Fisher, D. J., Blais, C. M., ... Horn, E. (2011). Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention. Biological Psychology, 88(1), pp. 83-93. doi:10.1016/j.biopsycho.2011.06.012.
Knott VJ, et al. Separate and Combined Effects of Low Dose Ketamine and Nicotine On Behavioural and Neural Correlates of Sustained Attention. Biol Psychol. 2011;88(1):83-93. PubMed PMID: 21742012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Separate and combined effects of low dose ketamine and nicotine on behavioural and neural correlates of sustained attention. AU - Knott,Verner J, AU - Millar,Anne M, AU - McIntosh,Judy F, AU - Shah,Dhrasti K, AU - Fisher,Derek J, AU - Blais,Crystal M, AU - Ilivitsky,Vadim, AU - Horn,Ed, Y1 - 2011/07/13/ PY - 2010/11/04/received PY - 2011/06/21/revised PY - 2011/06/24/accepted PY - 2011/7/12/entrez PY - 2011/7/12/pubmed PY - 2012/1/19/medline SP - 83 EP - 93 JF - Biological psychology JO - Biol Psychol VL - 88 IS - 1 N2 - Given the cognitive-promoting properties of the nicotinic acetylcholinergic receptor (nAChR) agonist, nicotine, the increased prevalence of smoke-inhaled nicotine in schizophrenia has been interpreted as an attempt to self-correct cognitive deficits, which have been particularly pronounced in the attentional domain. As glutamatergic abnormalities have been implicated in these attentional deficiencies, this study attempted to shed light on the separate and interactive roles of the N-methyl-d-aspartate receptor (NMDAR) and nAChR systems in the modulation of attention by investigating, in healthy volunteers, the separate and combined effects of nicotine and the NMDAR antagonist ketamine on neural and behavioural responses in a sustained attention task. In a randomized, double-blind, placebo controlled study, performance and the P300 event-related brain potential (ERP) in a visual information processing (RVIP) task were examined in 20 smokers and 20 non-smokers (both male and female). Assessment involved intravenous injection of a low subperceptual bolus dose (.04mg/kg) of ketamine or placebo, which was accompanied by acute treatment with nicotine (4mg) or placebo gum. Nicotine-enhanced attentional processing was most evident in nonsmokers, with both performance accuracy and P300 amplitude measures. Ketamine's detrimental effects on these behavioural and electrophysiologic measures were negatively moderated by acute nicotine, the synergistic effects being expressed differently in smokers and nonsmokers. These findings support the view that acute alterations and individual differences in nAChR function can moderate even subtle glutamatergic-driven cognitive deficiencies in schizophrenia and can be important therapeutic targets for treating cognitive impairments in schizophrenia. SN - 1873-6246 UR - https://www.unboundmedicine.com/medline/citation/21742012/Separate_and_combined_effects_of_low_dose_ketamine_and_nicotine_on_behavioural_and_neural_correlates_of_sustained_attention_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-0511(11)00156-6 DB - PRIME DP - Unbound Medicine ER -