Abstract
Rationale
People with tobacco addiction have deficits in cognition, in particular deficits in attention. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance.
Methods
Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration.
Conclusions
We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abarkan M, Fois GR, Vouillac-Mendoza C, Ahmed SH, Guillem K (2023) Altered neuronal activity in the ventromedial prefrontal cortex drives nicotine intake escalation. Neuropsychopharmacology 48(6):887–896
Ahmed SH (2012) The science of making drug-addicted animals. Neuroscience 211:107–125
Amitai N, Markou A (2009) Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration. Psychopharmacology 202(1–3):275–286
Bizarro L, Patel S, Murtagh C, Stolerman IP (2004) Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate. Behav Pharmacol 15(3):195–206
Blondel A, Simon H, Sanger DJ, Moser P (1999) The effect of repeated nicotine administration on the performance of drug-naive rats in a five-choice serial reaction time task. Behav Pharmacol 10(6–7):665–673
Briand LA, Flagel SB, Garcia-Fuster MJ, Watson SJ, Akil H, Sarter M et al (2008) Persistent alterations in cognitive function and prefrontal dopamine D2 receptors following extended, but not limited, access to self-administered cocaine. Neuropsychopharmacology 33(12):2969–2980
Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28(7):771–784
Dalley JW, Laane K, Pena Y, Theobald DE, Everitt BJ, Robbins TW (2005) Attentional and motivational deficits in rats withdrawn from intravenous self-administration of cocaine or heroin. Psychopharmacology 182(4):579–587
Diergaarde L, Pattij T, Poortvliet I, Hogenboom F, de Vries W, Schoffelmeer AN et al (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats. Biol Psychiat 63(3):301–308
Grundey J, Thirugnanasambandam N, Kaminsky K, Drees A, Skwirba AC, Lang N et al (2012) Neuroplasticity in cigarette smokers is altered under withdrawal and partially restituted by nicotine exposition. J Neurosci 32(12):4156–4162
Hahn B, Stolerman IP (2002) Nicotine-induced attentional enhancement in rats: effects of chronic exposure to nicotine. Neuropsychopharmacology 27(5):712–722
Hahn B, Shoaib M, Stolerman IP (2002) Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands. Psychopharmacology 162(2):129–137
Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210(4):453–469
Lerman C, LeSage MG, Perkins KA, O’Malley SS, Siegel SJ, Benowitz NL et al (2007) Translational research in medication development for nicotine dependence. Nat Rev Drug Discov 6(9):746–762
Levin ED, Simon BB (1998) Nicotinic acetylcholine involvement in cognitive function in animals. Psychopharmacology 138(3–4):217–230
Myers CS, Taylor RC, Moolchan ET, Heishman SJ (2008) Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray. Neuropsychopharmacology 33(3):588–598
Patterson F, Jepson C, Loughead J, Perkins K, Strasser AA, Siegel S et al (2010) Working memory deficits predict short-term smoking resumption following brief abstinence. Drug Alcohol Depend 106(1):61–64
Powell J, Dawkins L, West R, Powell J, Pickering A (2010) Relapse to smoking during unaided cessation: clinical, cognitive and motivational predictors. Psychopharmacology 212(4):537–549
Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163(3–4):362–380
Semenova S, Stolerman IP, Markou A (2007) Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats. Pharmacol Biochem Behav 87(3):360–368
Shoaib M, Bizarro L (2005) Deficits in a sustained attention task following nicotine withdrawal in rats. Psychopharmacology 178(2–3):211–222
Stolerman IP, Naylor CG, Mesdaghinia A, Morris HV (2009) The duration of nicotine-induced attentional enhancement in the five-choice serial reaction time task: lack of long-lasting cognitive improvement. Behav Pharmacol 20(8):742–754
Vanderschuren LJ, Ahmed SH (2013) Animal studies of addictive behavior. Cold Spring Harb Perspect Med 3(4):a011932
Vanderschuren L, Ahmed SH (2021) Animal models of the behavioral symptoms of substance use disorders. Cold Spring Harb Perspect Med 11(8):a040287. https://doi.org/10.1101/cshperspect.a040287
Vouillac-Mendoza C, Durand A, Ahmed SH, Guillem K (2024) Knowledge by omission: the significance of omissions in the 5-choice serial reaction time task. Psychopharmacology (Berl). https://doi.org/10.1007/s00213-024-06564-2
Winstanley CA, Bachtell RK, Theobald DE, Laali S, Green TA, Kumar A et al (2009) Increased impulsivity during withdrawal from cocaine self-administration: role for DeltaFosB in the orbitofrontal cortex. Cereb Cortex 19(2):435–444
Funding
This work was supported by the French Research Council (CNRS), the Université de Bordeaux, and the French National Agency (ANR- 15-CE37-0008–01; K.G.).
Author information
Authors and Affiliations
Contributions
K.G. designed research and experiments; C.V.M. and K.G. performed behavioral experiments and associated data analysis; K.G. and S.H.A. wrote the paper.
Corresponding author
Ethics declarations
Disclosure
The authors have nothing to disclose.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary Table 1
(PNG 34 kb)
Supplementary Table 2
(PNG 46 kb)
Supplementary Table 3
(PNG 67 kb)
Supplementary Table 4
(PNG 61 kb)
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Vouillac-Mendoza, C., Ahmed, S.H. & Guillem, K. Bidirectional relationship between attentional deficits and escalation of nicotine intake in male rats. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06604-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00213-024-06604-x