Modafinil and Memory: Effects of Modafinil on Morris Water Maze Learning and Pavlovian Fear Conditioning

Overview

Journal Behav Neurosci

Publisher American Psychological Association

Specialty Psychology

Date 2009 Apr 1

PMID 19331449

Citations 33

Authors

Tristan Shuman

Suzanne C Wood

Stephan G Anagnostaras

Affiliations

Soon will be listed here.

Abstract

Modafinil has been shown to promote wakefulness and some studies suggest the drug can improve cognitive function. Because of many similarities, the mechanism of action may be comparable to classical psychostimulants, although the exact mechanisms of modafinil's actions in wakefulness and cognitive enhancement are unknown. The current study aims to further examine the effects of modafinil as a cognitive enhancer on hippocampus-dependent memory in mice. A high dose of modafinil (75 mg/kg ip) given before training improved acquisition on a Morris water maze. When given only before testing, modafinil did not affect water maze performance. We also examined modafinil (0.075 to 75 mg/kg) on Pavlovian fear conditioning. A low dose of pretraining modafinil (0.75 mg/kg) enhanced memory of contextual fear conditioning (tested off-drug 1 week later) whereas a high dose (75 mg/kg) disrupted memory. Pretraining modafinil did not affect cued conditioning at any dose tested, and immediate posttraining modafinil had no effect on either cued or contextual fear. These results suggest that modafinil's effects of memory are more selective than amphetamine or cocaine and specific to hippocampus-dependent memory.

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References

Pigeau , Naitoh , Buguet , McCann , BARANSKI , Taylor . Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature. J Sleep Res. 1995; 4(4):212-228. DOI: 10.1111/j.1365-2869.1995.tb00172.x. View

Fanselow M . Conditioned and unconditional components of post-shock freezing. Pavlov J Biol Sci. 1980; 15(4):177-82. DOI: 10.1007/BF03001163. View

Anagnostaras S, Gale G, Fanselow M . Hippocampus and contextual fear conditioning: recent controversies and advances. Hippocampus. 2001; 11(1):8-17. DOI: 10.1002/1098-1063(2001)11:1<8::AID-HIPO1015>3.0.CO;2-7. View

Ferraro L, Antonelli T, OConnor W, Tanganelli S, Rambert F, Fuxe K . Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers. Biol Psychiatry. 1998; 42(12):1181-3. DOI: 10.1016/s0006-3223(97)00353-3. View

Rawson R, Shoptaw S, Ling W . Management of methamphetamine abuse and dependence. Curr Psychiatry Rep. 2006; 8(5):345-54. DOI: 10.1007/s11920-006-0035-x. View

Wisor J, Nishino S, Sora I, Uhl G, Mignot E, Edgar D . Dopaminergic role in stimulant-induced wakefulness. J Neurosci. 2001; 21(5):1787-94. PMC: 6762940. View

Anagnostaras S, Josselyn S, Frankland P, Silva A . Computer-assisted behavioral assessment of Pavlovian fear conditioning in mice. Learn Mem. 2000; 7(1):58-72. PMC: 311321. DOI: 10.1101/lm.7.1.58. View

Pack A, Black J, Schwartz J, Matheson J . Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med. 2001; 164(9):1675-81. DOI: 10.1164/ajrccm.164.9.2103032. View

Turner D, Robbins T, Clark L, Aron A, Dowson J, Sahakian B . Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl). 2002; 165(3):260-9. DOI: 10.1007/s00213-002-1250-8. View

10.

Kaufman K, Menza M, Fitzsimmons A . Modafinil monotherapy in depression. Eur Psychiatry. 2002; 17(3):167-9. DOI: 10.1016/s0924-9338(02)00646-6. View

11.

Wood S, Fay J, Sage J, Anagnostaras S . Cocaine and Pavlovian fear conditioning: dose-effect analysis. Behav Brain Res. 2006; 176(2):244-50. PMC: 1822737. DOI: 10.1016/j.bbr.2006.10.008. View

12.

Madras B, Xie Z, Lin Z, Jassen A, Panas H, Lynch L . Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther. 2006; 319(2):561-9. DOI: 10.1124/jpet.106.106583. View

13.

Clark R, Broadbent N, Squire L . Hippocampus and remote spatial memory in rats. Hippocampus. 2004; 15(2):260-72. PMC: 2754168. DOI: 10.1002/hipo.20056. View

14.

Wood S, Anagnostaras S . Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice. Psychopharmacology (Berl). 2008; 202(1-3):197-206. PMC: 2884195. DOI: 10.1007/s00213-008-1185-9. View

15.

Ferraro L, Fuxe K, Tanganelli S, Fernandez M, Rambert F, Antonelli T . Amplification of cortical serotonin release: a further neurochemical action of the vigilance-promoting drug modafinil. Neuropharmacology. 2000; 39(11):1974-83. DOI: 10.1016/s0028-3908(00)00019-8. View

16.

Steele R, Morris R . Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5. Hippocampus. 1999; 9(2):118-36. DOI: 10.1002/(SICI)1098-1063(1999)9:2<118::AID-HIPO4>3.0.CO;2-8. View

17.

Deroche-Gamonet V, Darnaudery M, Piat F, Le Moal M, Piazza P . Study of the addictive potential of modafinil in naive and cocaine-experienced rats. Psychopharmacology (Berl). 2002; 161(4):387-95. DOI: 10.1007/s00213-002-1080-8. View

18.

Morris R . Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984; 11(1):47-60. DOI: 10.1016/0165-0270(84)90007-4. View

19.

Roth T, Roehrs T . Etiologies and sequelae of excessive daytime sleepiness. Clin Ther. 1996; 18(4):562-76; discussion 561. DOI: 10.1016/s0149-2918(96)80207-4. View

20.

Brower V . Loosening addiction's deadly grip. Recent research paints a picture of addiction as a progressive, chronic neurological disease that wreaks havoc with brain chemistry. EMBO Rep. 2006; 7(2):140-2. PMC: 1369263. DOI: 10.1038/sj.embor.7400635. View