Modulation of fronto-cortical activity by modafinil: A functional imaging and Fos study in the rat

Neuropsychopharmacology

Volumn 37, Issue 3, 2012, Pages 822-837

  Gozzi, Alessandro ^a   Colavito, Valeria ^b   Seke Etet, Paul F ^b   Montanari, Dino ^c   Fiorini, Silvia ^b   Tambalo, Stefano ^b   Bifone, Angelo ^a   Zucconi, Gigliola Grassi ^b   Bentivoglio, Marina ^b  

^a CENTER FOR NANOTECHNOLOGY INNOVATION NEST   (Italy)

^b UNIVERSITY OF VERONA   (Italy)

^c GSK   (Italy)

Author keywords

cognition; EEG; fMRI; fronto cortical areas; pharmacological MRI; psychostimulant drugs

Indexed keywords

DOPAMINE; MODAFINIL; PROTEIN FOS;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AROUSAL; ARTICLE; BRAIN MAPPING; BRAIN REGION; CINGULATE GYRUS; COGNITION; CONTROLLED STUDY; CORPUS STRIATUM; DELTA RHYTHM; DIENCEPHALON; DORSAL RAPHE NUCLEUS; ELECTROENCEPHALOGRAPHY; FRONTAL CORTEX; HIPPOCAMPUS; IMMUNOREACTIVITY; MALE; NERVE CELL NETWORK; NERVE PROJECTION; NEUROMODULATION; NONHUMAN; NUCLEUS ACCUMBENS; PREFRONTAL CORTEX; PRIORITY JOURNAL; RAT; SOMATOSENSORY CORTEX; THALAMUS; THETA RHYTHM; WAKEFULNESS;

ANIMALS; BENZHYDRYL COMPOUNDS; BRAIN MAPPING; CENTRAL NERVOUS SYSTEM STIMULANTS; FRONTAL LOBE; MAGNETIC RESONANCE IMAGING; MALE; NERVE NET; PROTO-ONCOGENE PROTEINS C-FOS; RATS; RATS, SPRAGUE-DAWLEY; SOMATOSENSORY CORTEX;

EID: 84855875195     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2011.260     Document Type: Article

References (110)

1. Antunes LM, Golledge HD, Roughan JV, Flecknell PA (2003). Comparison of electroencephalogram activity and auditory evoked responses during isoflurane and halothane anaesthesia in the rat. Vet Anaesth Analg 30:15-23. (Pubitemid 36154131)
2. Baranski JV, Pigeau R, Dinich P, Jacobs I (2004). Effects of modafinil on cognitive and meta-cognitive performance. Hum Psychopharmacol 19:323-332. (Pubitemid 39106873)
3. Becker JT, Olton DS, Anderson CA, Breitinger ERP (1981). Cognitive mapping in rats: the role of the hippocampal and frontal systems in retention and reversal. Behav Brain Res 3:1-22. (Pubitemid 11117773)
4. Beracochea D, Cagnard B, Celerier A, le MJ, Peres M, Pierard C (2001). First evidence of a delay-dependent working memoryenhancing effect of modafinil in mice. NeuroReport 12:375-378. (Pubitemid 32114383)
5. Beracochea D, Celerier A, Peres M, Pierard C (2003). Enhancement of learning processes following an acute modafinil injection in mice. Pharmacol Biochem Behav 76:473-479. (Pubitemid 37487903)
6. Berridge CW (2006). Neural substrates of psychostimulantinduced arousal. Neuropsychopharmacology 31:2332-2340.
7. Berridge CW, Foote SL (1991). Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus. J Neurosci 11:3135-3145.
8. Berridge CW, Morris MF (2000). Amphetamine-induced activation of forebrain EEG is prevented by noradrenergic beta-receptor blockade in the halothane-anesthetized rat. Psychopharmacology 148:307-313. (Pubitemid 30136738)
9. Bifone A, Gozzi A (2010). Functional and pharmacological MRI in understanding brain function. In: Hagan J (ed) Molecular and Functional Models in Neuropsychiatry. Springer, Berlin. pp 323-357.
10. Bifone A, Gozzi A, Schwarz AJ (2010). Functional connectivity in the rat brain: a complex network approach. Magn Reson Imaging 28:1200-1209.
11. Birbaumer N, Murguialday AR, Cohen L (2008). Brain-computer interface in paralysis. Curr Opin Neurol 21:634-638.
12. Block AE, Dhanji H, Thompson-Tardif SF, Floresco SB (2007). Thalamic-prefrontal cortical-ventral striatal circuitry mediates dissociable components of strategy set shifting. Cereb Cortex 17:1625-1636.
13. Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM (1995). MR contrast due to intravascular magnetic susceptibility perturbations. Magn Reson Med 34:555-566.
14. Cirelli C, Tononi G (2000). On the functional significance of c-fos induction during the sleep-waking cycle. Sleep 23:453-469. (Pubitemid 30409232)
15. Dalley JW, Cardinal RN, Robbins TW (2004). Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771-784. (Pubitemid 39535871)
16. Dawson N, Thompson RJ, McVie A, Thomson DM, Morris BJ, Pratt JA (2010). Modafinil reverses phencyclidine-induced deficits in cognitive flexibility, cerebral metabolism, and functional brain connectivity. Schizophr Bull: doi: 10.1093/schbul/sbq090.
17. Deakin JFW, Lees J, McKie S, Hallak JEC, Williams SR, Dursun SM (2008). Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry 65:154-164. (Pubitemid 351214314)
18. de Saint HZ, Orosco M, Rouch C, Blanc G, Nicolaidis S (2001). Variations in extracellular monoamines in the prefrontal cortex and medial hypothalamus after modafinil administration: a microdialysis study in rats. NeuroReport 12:3533-3537. (Pubitemid 33065493)
19. Duncan GE, Miyamoto S, Leipzig JN, Lieberman JA (1999). Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine. Brain Res 843:171-183. (Pubitemid 29488707)
20. Engber TM, Dennis SA, Jones BE, Miller MS, Contreras PC (1998). Brain regional substrates for the actions of the novel wakepromoting agent modafinil in the rat: comparison with amphetamine. Neuroscience 87:905-911. (Pubitemid 28400361)
21. Espana RA, Scammell TE (2004). Sleep neurobiology for the clinician. Sleep 27:811-820. (Pubitemid 38823381)
22. Ferrari L, Crestan V, Sabattini G, Vinco F, Fontana S, Gozzi A (2010). Brain penetration of local anaesthetics in the rat: Implications for experimental neuroscience. J Neurosci Methods 186:143-149.
23. Ferraro L, Fuxe K, Tanganelli S, Tomasini MC, Rambert FA, Antonelli T (2002). Differential enhancement of dialysate serotonin levels in distinct brain regions of the awake rat by modafinil: possible relevance for wakefulness and depression. J Neurosci Res 68:107-112. (Pubitemid 34275003)
24. Fiocchi EM, Lin YG, Aimone L, Gruner JA, Flood DG (2009). Armodafinil promotes wakefulness and activates Fos in rat brain. Pharm Biochem Behav 92:549-557.
25. Floresco SB, Ghods-Sharifi S, Vexelman C, Magyar O (2006). Dissociable roles for the nucleus accumbens core and shell in regulating set shifting. J Neurosci 26:2449-2457. (Pubitemid 44699005)
26. Fox MT, Barense MD, Baxter MG (2003). Perceptual attentional set-shifting is impaired in rats with neurotoxic lesions of posterior parietal cortex. J Neurosci 23:676-681. (Pubitemid 36139566)
27. Freudenreich O, Henderson DC, Macklin EA, Evins AE, Fan X, Cather C et al. (2009). Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. J Clin Psychiatry 70:1674-1680.
28. Friston KJ, Jezzard P, Turner R (1994). Analysis of functional MRI time-series. Hum Brain Mapp 1:153-171.
29. Gaisler-Salomon I, Schobel SA, Small SA, Rayport S (2009). How high-resolution basal-state functional imaging can guide the development of new pharmacotherapies for schizophrenia. Schizophr Bull 35:1037-1044.
30. Gold LH, Balster RL (1996). Evaluation of the cocaine-like discriminative stimulus effects and reinforcing effects of modafinil. Psychopharmacology 126:286-292. (Pubitemid 26276699)
31. Gompf H, Chen J, Sun Y, Yanagisawa M, Aston-Jones G, Kelz MB (2009). Halothane-induced hypnosis is not accompanied by inactivation of orexinergic output in rodents. Anesthesiology 111:1001-1009.
32. Gozzi A, Ceolin L, Schwarz A, Reese T, Bertani S, Bifone A (2007). A multimodality investigation of cerebral haemodynamics and autoregulation in phMRI. Magn Reson Imaging 25:826-833. (Pubitemid 47081368)
33. Gozzi A, Crestan V, Turrini G, Clemens M, Bifone A (2010). Antagonism at serotonin 5-HT2A receptors modulates functional activity of frontohippocampal circuit. Psychopharmacology 209:37-50.
34. Gozzi A, Herdon H, Schwarz A, Bertani S, Crestan V, Turrini G et al. (2008a). Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology 201:273-284.
35. Gozzi A, Large C, Schwarz A, Bertani S, Crestan V, Bifone A (2008b). Differential effects of antipsychotic and glutamatergic agents on the phMRI response to phencyclidine. Neuropsychopharmacology 33:1690-1703. (Pubitemid 351684709)
36. Gozzi A, Massagrande M, Amantini D, Antolini M, Martinelli P, Cesari N et al. (2011). Functional magnetic resonance imaging reveals different neural substrates for the effects of orexin-1 and orexin-2 receptor antagonists. PLoS One 6:1e16406.
37. Gozzi A, Schwarz A, Reese T, Bertani S, Crestan V, Bifone A (2006). Region-specific effects of nicotine on brain activity: a pharmacological MRI study in the drug-näive rat. Neuropsychopharmacology 31:1690-1703. (Pubitemid 44106700)
38. Gozzi A, Schwarz AJ, Reese T, Crestan V, Bifone A (2008c). Drug-anaesthetic interaction in phMRI: the case of the pyschotomimetic agent phencyclidine. Magn Reson Imaging 26:999-1006.
39. Grassi-Zucconi G, Giuditta A, Mandile P, Chen S, Vescia S, Bentivoglio M (1994). c-fos spontaneous expression during wakefulness is reversed during sleep in neuronal subsets of the rat cortex. J Physiol Paris 88:91-93. (Pubitemid 24120250)
40. Grunwald F, Schrock H, Kuschinsky W (1991). The influence of nicotine on local cerebral blood flow in rats. Neurosci Lett 124:108-110.
41. Honey G, Bullmore E (2004). Human pharmacological MRI. Trends Pharm Sci 25:366-374. (Pubitemid 38829490)
42. Hudetz AG (2002). Effect of volatile anesthetics on interhemispheric EEG cross-approximate entropy in the rat. Brain Res 954:123-131. (Pubitemid 35223448)
43. Hunter MD, Ganesan V, Wilkinson ID, Spence SA (2006). Impact of modafinil on prefrontal executive function in schizophrenia. Am J Psychiatry 163:2184-2186. (Pubitemid 46114242)
44. Jasinski DR (2000). An evaluation of the abuse potential of modafinil using methylphenidate as a reference. J Psychopharmacol 14:53-60. (Pubitemid 30156539)
45. Joo EY, Tae WS, Jung KY, Hong SB (2008). Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study. J Sleep Res 17:82-88. (Pubitemid 351239354)
46. Kruszewski SP (2006). Euphorigenic and abusive properties of modafinil. Am J Psychiatry 163:549.
47. Kumar R (2008). Approved and investigational uses of modafinil: an evidence-based review. Drugs 68:1803-1839.
48. Langsjo JW, Kaisti KK, Aalto S, Hinkka S, Aantaa R, Oikonen V et al. (2003). Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 99:614-623. (Pubitemid 37051976)
49. Lin JS, Gervasoni D, Hou Y, Vanni-Mercier G, Rambert F, Frydman A (2000). Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat. J Sleep Res 9:89-96. (Pubitemid 30195298)
50. Lin JS, Hou Y, Jouvet M (1996). Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat. Proc Natl Acad Sci USA 93:14128-14133. (Pubitemid 26424257)
51. Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature 412:150-157. (Pubitemid 32674704)
52. Lynch G, Palmer LC, Gall CM (2011). The likelihood of cognitive enhancement. Pharmacol Biochem Behav 99:116-129.
53. Madras BK, Xie Z, Lin Z, Jassen A, Panas H, Lynch L et al. (2006). Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther 319:561-569.
54. Mandeville JB, Marota JJA, Kosofsky BE, Keltner JR, Weissleder R, Rosen B et al. (1998). Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation. Magn Reson Med 39:615-624. (Pubitemid 28150996)
55. Marota JJ, Crosby G, Uhl GR (1992). Selective effects of pentobarbital and halothane on c-fos and jun-B gene expression in rat brain. Anesthesiology 77:365-371.
56. Mathieu-Kia AM, Pages C, Besson MJ (1998). Inducibility of c-Fos protein in visuo-motor system and limbic structures after acute and repeated administration of nicotine in the rat. Synapse 29:343-354. (Pubitemid 28328678)
57. McClellan KJ, Spencer CM (1998). Modafinil: a review of its pharmacology and clinical efficacy in the management of narcolepsy. CNS Drugs 9:311-324. (Pubitemid 28210366)
58. McCormick DA, Bal T (1997). Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185-215. (Pubitemid 27106380)
59. Mesulam MM (1990). Large-scale neurocognitive networks and distributed processing for attention, language, and memory. Ann Neurol 28:597-613.
60. Minzenberg MJ, Carter CS (2007). Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 33:1477-1502.
61. Morrison PD, Nottage J, Stone JM, Bhattacharyya S, Tunstall N, Brenneisen R et al. (2011). Disruption of frontal theta coherence by [delta]9- tetrahydrocannabinol is associated with positive psychotic symptoms. Neuropsychopharmacology 36:827-836.
62. Murillo-Rodriguez E, Haro R, Palomero-Rivero M, Millan-Aldaco D, Drucker-Colin R (2007). Modafinil enhances extracellular levels of dopamine in the nucleus accumbens and increases wakefulness in rats. Behav Brain Res 176:353-357. (Pubitemid 44895428)
63. Myrick H, Malcolm R, Taylor B, LaRowe S (2004). Modafinil: preclinical, clinical, and post-marketing surveillance-a review of abuse liability issues. Ann Clin Psychiatry 16:101-109. (Pubitemid 39089110)
64. Newman JL, Negus SS, Lozama A, Prisinzano TE, Mello NK (2010). Behavioral evaluation of modafinil and the abuse-related effects of cocaine in rhesus monkeys. Exp Clin Psychopharmacol 18:395-408.
65. Novikova NS, Kazakova TB, Rogers V, Korneva EA (2004). Expression of the c-fos gene in spinal cord and brain cells in rats subjected to stress in conditions of exposure to various types of halothane anesthesia. Neurosci Behav Phys 34:407-412. (Pubitemid 39137411)
66. Pace-Schott EF, Hobson JA (2002). The neurobiology of sleep: genetics, cellular physiology and subcortical networks. Nat Rev Neurosci 3:591-605. (Pubitemid 135706668)
67. Paxinos G, Watson C (2005). The Rat Brain in Stereotaxic Coordinates, 5th edn, Elsevier, Berlin.
68. Pepelko WE, Dixon GA (1975). Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both. J Appl Physiol 38:581-587.
69. Pierre JM, Peloian JH, Wirshing DA, Wirshing WC, Marder SR (2007). A randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia. J Clin Psychiatry 68:705-710. (Pubitemid 46841853)
70. Pigeau R, Naitoh P, Buguet A, McCann C, Baranski J, Taylor M (1995). Modafinil, d-amphetamine and placebo during sustained mental work: Effects on mood, fatigue, cognitive performance and body temperature. J Sleep Res 4:212-228. (Pubitemid 26010119)
71. Qu WM, Huang ZL, Xu XH, Matsumoto N, Urade Y (2008). Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. J Neurosci 28:8462-8469.
72. Ramos-Cabrer P, Weber R, Wiedermann D, Hoehn M (2005). Continuous noninvasive monitoring of transcutaneous blood gases for a stable and persistent BOLD contrast in fMRI studies in the rat. NMR Biomed 18:440-446. (Pubitemid 41646185)
73. Repantis D, Schlattmann P, Laisney O, Heuser I (2010). Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res 62:187-206.
74. Salamone JD, Correa M (2002). Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3-25. (Pubitemid 35346426)
75. Saletu M, Anderer P, Saletu-Zyhlarz GM, Mandl M, Arnold O, Zeitlhofer J (2004). EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil. J Neurol 251:1354-1363.
76. Saletu M, Anderer P, Semlitsch HV, Saletu-Zyhlarz GM, Mandl M, Zeitlhofer J (2007). Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions linked to psychometric performance under modafinil in narcolepsy. Psychiatry Res 154:69-84. (Pubitemid 46072707)
77. Scammell TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS (2000). Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 20:8620-8628.
78. Schwarz AJ, Danckaert A, Reese T, Gozzi A, Paxinos G, Watson C et al. (2006a). A stereotaxic MRI template set for the rat brain with tissue class distribution maps and co-registered anatomical atlas: application to pharmacological MRI. Neuroimage 32:538-550. (Pubitemid 44149167)
79. Schwarz AJ, Gozzi A, Bifone A (2009). Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI. Neuroimage 47:302-311.
80. Schwarz AJ, Gozzi A, Reese T, Bifone A (2007a). Functional connectivity in the pharmacologically activated brain: resolving networks of correlated responses to d-amphetamine. Magn Reson Med 57:704-713. (Pubitemid 46731796)
81. Schwarz AJ, Gozzi A, Reese T, Bifone A (2007b). In vivo mapping of functional connectivity in neurotransmitter systems using pharmacological MRI. Neuroimage 34:1627-1636. (Pubitemid 46187087)
82. Schwarz AJ, Reese T, Gozzi A, Bifone A (2003). Functional MRI using intravascular contrast agents: detrending of the relative cerebrovascular (rCBV) time course. Magn Reson Imaging 21:1191-1200. (Pubitemid 38199724)
83. Schwarz AJ, Whitcher B, Gozzi A, Reese T, Bifone A (2006b). Studylevel wavelet cluster analysis and data-driven signal models in pharmacological MRI. J Neurosci Methods 159:346-360. (Pubitemid 44920262)
84. Shea JL, Mochizuki T, Sagvaag V, Aspevik T, Bjorkum AA, Datta S (2008). Rapid eye movement (REM) sleep homeostatic regulatory processes in the rat: changes in the sleep-wake stages and electroencephalographic power spectra. Brain Res 1213:48-56.
85. Small SA, Chawla MK, Buonocore M, Rapp PR, Barnes CA (2004). Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc Natl Acad Sci USA 101:7181-7186. (Pubitemid 38596463)
86. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H et al. (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23 (Suppl 1): S208-S219. (Pubitemid 39421720)
87. Spence SA, Green RD, Wilkinson ID, Hunter MD (2005). Modafinil modulates anterior cingulate function in chronic schizophrenia. Br J Psychiatry 187:55-61. (Pubitemid 41002514)
88. Squire LR (1992). Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99:195-231.
89. Stark JA, Davies KE, Williams SR, Luckman SM (2006). Functional magnetic resonance imaging and c-Fos mapping in rats following an anorectic dose of m-chlorophenylpiperazine. Neuroimage 31:1228-1237. (Pubitemid 43851328)
90. Stein EA, Pankiewicz J, Harsch HH, Cho JK, Fuller SA, Hoffmann RG et al. (1998). Nicotine-induced limbic cortical activation in the human brain: a functional MRI study. Am J Psychiatry 155:1009-1015. (Pubitemid 28357723)
91. Steriade M (1996). Arousal: revisiting the reticular activating system. Science 272:225-226. (Pubitemid 26119135)
92. Steriade M, Amzica F, Contreras D (1994). Cortical and thalamic cellular correlates of electroencephalographic burst-suppression. Electroenceph Clin Neurophysiol 90:1-16. (Pubitemid 24057704)
93. Stoops W, Lile J, Fillmore M, Glaser P, Rush C (2005). Reinforcing effects of modafinil: influence of dose and behavioral demands following drug administration. Psychopharmacology 182:186-193. (Pubitemid 41400876)
94. Sumner BEH, Cruise LA, Slattery DA, Hill DR, Shahid M, Henry B (2004). Testing the validity of c-fos expression profiling to aid the therapeutic classification of psychoactive drugs. Psychopharmacology 171:306-321. (Pubitemid 38200069)
95. Sun WZ, Shyu BC, Shieh JY (1996). Nitrous oxide or halothane, or both, fail to suppress c-fos expression in rat spinal cord dorsal horn neurones after subcutaneous formalin. Br J Anaesth 76:99-105. (Pubitemid 26030224)
96. Thomas RJ, Kwong K (2006). Modafinil activates cortical and subcortical sites in the sleep-deprived state. Sleep 29:1471-1481. (Pubitemid 44764674)
97. Tsanov M, Lyons DG, Barlow S, Gonzßlez Reyes RE, O'Mara SM (2007). The psychostimulant modafinil facilitates water maze performance and augments synaptic potentiation in dentate gyrus. Neuropharmacology 59:9-19.
98. Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003). Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology 165:260-269. (Pubitemid 36197601)
99. Uylings HB, Groenewegen HJ, Kolb B (2003). Do rats have a prefrontal cortex? Behav Brain Res 146:3-17. (Pubitemid 37476129)
100. Vanderwolf CH (1992). The electrocorticogram in relation to physiology and behavior: A new analysis. Electroenceph Clin Neurophysiol 82:165-175.
101. Vertes RP (2006). Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142:1-20. (Pubitemid 44353937)
102. Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F et al. (2009). Effects of modafinil on dopamine and dopamine transporters in the male human brain. JAMA 301:1148-1154.
103. Weiergrasber M, Henry M, Hescheler J, Smyth N, Schneider T (2005). Electrocorticographic and deep intracerebral EEG recording in mice using a telemetry system. Brain Res Protoc 14:154-164. (Pubitemid 40431695)
104. Wesensten NJ, Belenky G, Kautz MA, Thorne DR, Reichardt RM, Balkin TJ (2002). Maintaining alertness and performance during sleep deprivation: modafinil vs caffeine. Psychopharmacology 159:238-247. (Pubitemid 34143372)
105. Willie JT, Renthal W, Chemelli RM, Miller MS, Scammell TE, Yanagisawa M (2005). Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience 130:983-995. (Pubitemid 40094630)
106. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001). Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21:1787-1794. (Pubitemid 32184295)
107. Wong YN, Simcoe D, Hartman LN, Laughton WB, King SP, McCormick GC (1999). A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers. J Clin Pharmacol 39:30-40. (Pubitemid 29053150)
108. Worsley KJ, Evans AC, Marrett S, Neelin P (1992). A threedimensional statistical analysis for CBF activation studies in human brain. J Cereb Blood Flow Metab 12:900-918.
109. Yu E, Chovan JP, Ring SC, Robertson P (2000). Pharmacokinetics of modafinil enantiomers in rats. AAPS J 2:3337-3340.
110. Zaharchuk G, Mandeville JB, Bogdanov Jr AA, Weissleder R, Rosen BR, Marota JJ (1999). Cerebrovascular dynamics of autoregulation and hypoperfusion. An MRI study of CBF and changes in total and microvascular cerebral blood volume during hemorrhagic hypotension. Stroke 30:2197-2204.