medial forebrain bundle


Summary: A complex group of fibers arising from the basal olfactory regions, the periamygdaloid region, and the septal nuclei, and passing to the lateral hypothalamus. Some fibers continue into the tegmentum.

Top Publications

  1. Cho B, Song D, Sugama S, Shin D, Shimizu Y, Kim S, et al. Pathological dynamics of activated microglia following medial forebrain bundle transection. Glia. 2006;53:92-102 pubmed
    ..the phagocytic, immunophenotypic, morphological, and migratory properties of activated microglia in the medial forebrain bundle (MFB) axotomized rat brain...
  2. Cho B, Sugama S, Shin D, DeGiorgio L, Kim S, Kim Y, et al. Microglial phagocytosis of dopamine neurons at early phases of apoptosis. Cell Mol Neurobiol. 2003;23:551-60 pubmed
    Transection of the medial forebrain bundle caused apoptosis of dopamine neurons in the rat substantia nigra...
  3. Coenen V, Honey C, Hurwitz T, Rahman A, McMaster J, Bürgel U, et al. Medial forebrain bundle stimulation as a pathophysiological mechanism for hypomania in subthalamic nucleus deep brain stimulation for Parkinson's disease. Neurosurgery. 2009;64:1106-14; discussion 1114-5 pubmed publisher
    ..We suggest a different explanation, in which the coactivation of the medial forebrain bundle (MFB), outside the STN, leads to hypomania during STN DBS...
  4. Lavin A, Nogueira L, Lapish C, Wightman R, Phillips P, Seamans J. Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling. J Neurosci. 2005;25:5013-23 pubmed
  5. Easton A, Gaffan D. Crossed unilateral lesions of the medial forebrain bundle and either inferior temporal or frontal cortex impair object-reward association learning in Rhesus monkeys. Neuropsychologia. 2001;39:71-82 pubmed
    ..and midbrain structures, while sparing cortical white matter, by crossed unilateral lesions of the medial forebrain bundle in one hemisphere and inferior temporal cortex in the opposite hemisphere...
  6. Coenen V, Panksepp J, Hurwitz T, Urbach H, Mädler B. Human medial forebrain bundle (MFB) and anterior thalamic radiation (ATR): imaging of two major subcortical pathways and the dynamic balance of opposite affects in understanding depression. J Neuropsychiatry Clin Neurosci. 2012;24:223-36 pubmed publisher
    The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression...
  7. Vorobyov V, Schibaev N, Morelli M, Carta A. EEG modifications in the cortex and striatum after dopaminergic priming in the 6-hydroxydopamine rat model of Parkinson's disease. Brain Res. 2003;972:177-85 pubmed
    In rats bearing a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, a single administration of a dopamine receptor agonist (priming) sensitizes the behavioral motor responses to a dopaminergic agonist, ..
  8. Pillolla G, Melis M, Perra S, Muntoni A, Gessa G, Pistis M. Medial forebrain bundle stimulation evokes endocannabinoid-mediated modulation of ventral tegmental area dopamine neuron firing in vivo. Psychopharmacology (Berl). 2007;191:843-53 pubmed
    ..whether back-propagating action potentials in dopamine (DA) neurons, evoked by the stimulation of the medial forebrain bundle (MFB), could trigger endocannabinoid-mediated forms of synaptic modulation...
  9. Galati S, Stanzione P, D Angelo V, Fedele E, Marzetti F, Sancesario G, et al. The pharmacological blockade of medial forebrain bundle induces an acute pathological synchronization of the cortico-subthalamic nucleus-globus pallidus pathway. J Physiol. 2009;587:4405-23 pubmed publisher the development of pathological synchronization, we performed a pharmacological inactivation of the medial forebrain bundle (MFB) through tetrodotoxin (TTX), which led to a dramatic, but reversible, reduction of the dopamine ..

More Information


  1. Liu L, Hsu S, Kalia S, Lozano A. Injury and strain-dependent dopaminergic neuronal degeneration in the substantia nigra of mice after axotomy or MPTP. Brain Res. 2003;994:243-52 pubmed
    ..Ten days later, these neurons were axotomized in the medial forebrain bundle (MFB) unilaterally or N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was administered ..
  2. Freitas K, Carroll F, Negus S. Comparison of effects produced by nicotine and the ?4?2-selective agonist 5-I-A-85380 on intracranial self-stimulation in rats. Exp Clin Psychopharmacol. 2016;24:65-75 pubmed publisher
    ..01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a ..
  3. Sagara H, Kitamura Y, Esumi S, Sendo T, Araki H, Gomita Y. Motivational effects of nicotine as measured by the runway method using priming stimulation of intracranial self-stimulation behavior. Acta Med Okayama. 2008;62:227-33 pubmed
    ..Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats...
  4. Cheer J, Wassum K, Heien M, Phillips P, Wightman R. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J Neurosci. 2004;24:4393-400 pubmed
    ..These data demonstrate that doses of a cannabinoid agonist known to increase burst firing produce ongoing fluctuations in extracellular dopamine on a previously unrecognized temporal scale in the nucleus accumbens. ..
  5. Wenner M, Kawamura N, Ishikawa T, Matsuda Y. Reward linked to increased natural killer cell activity in rats. Neuroimmunomodulation. 2000;7:1-5 pubmed
    ..In a pre-test study, all rats had demonstrated that the electrode site had self-stimulating properties, which supports the possibility that the experience of reward may be implicated in NK cell activity augmentation. ..
  6. Qin J, Wu M, Yu S, Gao X, Zhang J, Dong X, et al. Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease. Toxicol Lett. 2015;238:70-82 pubmed publisher
    ..also exerted protective effects in an in vivo PD model, which was created by rotenone injection into the medial forebrain bundle of rats...
  7. Samaha A, Li Y, Robinson T. The rate of intravenous cocaine administration determines susceptibility to sensitization. J Neurosci. 2002;22:3244-50 pubmed
    ..This suggests that the temporal dynamics of drug delivery to the brain is a critical factor in the ability of cocaine to induce forms of neuronal plasticity that may contribute to addiction. ..
  8. Nikkhah G, Falkenstein G, Rosenthal C. Restorative plasticity of dopamine neuronal transplants depends on the degree of hemispheric dominance. J Neurosci. 2001;21:6252-63 pubmed
  9. Grant R, Clarke P. Susceptibility of ascending dopamine projections to 6-hydroxydopamine in rats: effect of hypothermia. Neuroscience. 2002;115:1281-94 pubmed
    ..these questions, 6-OHDA or vehicle was infused into either the ventral or dorsal striatum or into the medial forebrain bundle, under conditions of brain normothermia or hypothermia...
  10. Kozlowski D, Miljan E, Bremer E, Harrod C, Gerin C, Connor B, et al. Quantitative analyses of GFRalpha-1 and GFRalpha-2 mRNAs and tyrosine hydroxylase protein in the nigrostriatal system reveal bilateral compensatory changes following unilateral 6-OHDA lesions in the rat. Brain Res. 2004;1016:170-81 pubmed
    ..nigra (SN) of normal rats and rats acutely or progressively lesioned by 6-OHDA injected into the medial forebrain bundle or ST, respectively. GFRalpha-1 mRNA was clearly detected in normal ST...
  11. Cheng H, Burke R. The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo. J Neurochem. 2010;113:683-91 pubmed publisher
    ..Therefore, Wld(S) offers axon protection, but it reveals fundamentally different processes underlying antero- and retrograde degeneration in this system. ..
  12. Heuer A, Dunnett S. Unilateral 6-OHDA lesions induce lateralised deficits in a 'skinner box' operant choice reaction time task in rats. J Parkinsons Dis. 2012;2:309-20 pubmed publisher most commonly modelled in rats via injection of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Assessment of lateralised choice reaction time is usually conducted in the 9 hole box, a highly ..
  13. Barnum C, Eskow K, Dupre K, Blandino P, Deak T, Bishop C. Exogenous corticosterone reduces L-DOPA-induced dyskinesia in the hemi-parkinsonian rat: role for interleukin-1beta. Neuroscience. 2008;156:30-41 pubmed publisher
    ..To do this, male Sprague-Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0-3...
  14. Silva I, Cortes H, Escartin E, Rangel C, Floran L, Erlij D, et al. L-DOPA inhibits depolarization-induced [3H]GABA release in the dopamine-denervated globus pallidus of the rat: the effect is dopamine independent and mediated by D2-like receptors. J Neural Transm (Vienna). 2006;113:1847-53 pubmed
    ..L-DOPA could control Parkinson's disease symptoms acting not only as dopamine precursor but also by itself. ..
  15. Sun W, Sugiyama K, Asakawa T, Yamaguchi H, Akamine S, Ouchi Y, et al. Dynamic changes of striatal dopamine D2 receptor binding at later stages after unilateral lesions of the medial forebrain bundle in Parkinsonian rat models. Neurosci Lett. 2011;496:157-62 pubmed publisher
    ..two different rat parkinsonian models, lesioning with 6-hydroxydopamine in the striatum and in the medial forebrain bundle (MFB)...
  16. Wang Q, Wang P, McLachlan C, Wong P. Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats. Brain Res. 2005;1045:229-33 pubmed
    Sprague-Dawley rats with unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine showed marked decrease in the expression of dopamine D1 and D2 receptors in the prefrontal cortex...
  17. Wilber A, Clark B, Forster T, Tatsuno M, McNaughton B. Interaction of egocentric and world-centered reference frames in the rat posterior parietal cortex. J Neurosci. 2014;34:5431-46 pubmed publisher
    ..We identified cells that exhibit the predicted egocentric-by-allocentric conjunctive characteristics and anticipate orienting toward the goal. ..
  18. Scherfler C, Donnemiller E, Schocke M, Dierkes K, Decristoforo C, Oberladstätter M, et al. Evaluation of striatal dopamine transporter function in rats by in vivo beta-[123I]CIT pinhole SPECT. Neuroimage. 2002;17:128-41 pubmed
    ..Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique. ..
  19. Kang Y, Jung H, Oh J, Song D. Use of PEGylated Immunoliposomes to Deliver Dopamine Across the Blood-Brain Barrier in a Rat Model of Parkinson's Disease. CNS Neurosci Ther. 2016;22:817-23 pubmed publisher
    ..DA, DA-PL, and DA-PIL by examining brain tissue in normal rats and rats that underwent transection of the medial forebrain bundle to induce PD...
  20. Bauer C, Banks M, Blough B, Negus S. Rate-dependent effects of monoamine releasers on intracranial self-stimulation in rats: implications for abuse liability assessment. Behav Pharmacol. 2013;24:448-58 pubmed publisher
  21. Truong L, Allbutt H, Kassiou M, Henderson J. Developing a preclinical model of Parkinson's disease: a study of behaviour in rats with graded 6-OHDA lesions. Behav Brain Res. 2006;169:1-9 pubmed
    Injection of increasing concentrations of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) can be used to establish a graded model of different clinical stages of Parkinson's disease (PD)...
  22. Rodriguez M, Morales I, González Mora J, Gomez I, Sabate M, Dopico J, et al. Different levodopa actions on the extracellular dopamine pools in the rat striatum. Synapse. 2007;61:61-71 pubmed
    ..This study suggests a different kinetic for levodopa action on the volume transmitter and neurotransmitter DA-pool, showing marked changes in levodopa action in the denervated striatum. ..
  23. Waraczynski M, Abbott S, Schultz A. CaV1.3 channel blockade in the extended amygdala has a delayed effect on the reward efficacy of medial forebrain bundle stimulation. Behav Brain Res. 2017;317:485-493 pubmed publisher
    ..that stimulating D2 dopamine receptors in the central sublenticular extended amygdala (SLEAc) can render medial forebrain bundle (MFB) stimulation less rewarding...
  24. Westin J, Janssen M, Sager T, Temel Y. Automated gait analysis in bilateral parkinsonian rats and the role of L-DOPA therapy. Behav Brain Res. 2012;226:519-28 pubmed publisher
    ..The bilateral neurotoxin injections into the medial forebrain bundle resulted in an average dopamine (DA) loss of 70% in each striata, which corresponds to the DA levels ..
  25. Lorenc Koci E, Gołembiowska K, Wardas J. 1,2,3,4-Tetrahydroisoquinoline protects terminals of dopaminergic neurons in the striatum against the malonate-induced neurotoxicity. Brain Res. 2005;1051:145-54 pubmed
    ..Injection of malonate at a dose of 3 mumol unilaterally into the rat left medial forebrain bundle resulted in the 54% decrease in dopamine (DA) concentration in the ipsilateral striatum and, depending on ..
  26. Hashemi P, Dankoski E, Wood K, Ambrose R, WIGHTMAN R. In vivo electrochemical evidence for simultaneous 5-HT and histamine release in the rat substantia nigra pars reticulata following medial forebrain bundle stimulation. J Neurochem. 2011;118:749-59 pubmed publisher
    ..technical challenges associated with rat DRN surgery by electrically stimulating 5-HT projections in the medial forebrain bundle (MFB), a more accessible anatomical location...
  27. Jia J, Sun Z, Li B, Pan Y, Wang H, Wang X, et al. Electro-acupuncture stimulation improves motor disorders in Parkinsonian rats. Behav Brain Res. 2009;205:214-8 pubmed publisher
    ..In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), the effects of EA stimulation were investigated...
  28. Eskow K, Dupre K, Barnum C, Dickinson S, Park J, Bishop C. The role of the dorsal raphe nucleus in the development, expression, and treatment of L-dopa-induced dyskinesia in hemiparkinsonian rats. Synapse. 2009;63:610-20 pubmed publisher
    ..In the first study, dual serotonin/dopamine selective lesions of the RRN and medial forebrain bundle, respectively, verified that the RRN are essential for the development of LID...
  29. Hernandez G, Haines E, Rajabi H, Stewart J, Arvanitogiannis A, Shizgal P. Predictable and unpredictable rewards produce similar changes in dopamine tone. Behav Neurosci. 2007;121:887-95 pubmed
    ..Nonetheless, indistinguishable changes in DA concentration were observed in the 2 groups. Thus, reward predictability had no discernable effect on a measure believed to track the slower components of DA signaling. ..
  30. Sarkaki A, Farbood Y, Dolatshahi M, Mansouri S, Khodadadi A. Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease. Acta Med Iran. 2016;54:494-502 pubmed
    ..6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA...
  31. Papathanou M, van der Laan R, Jenner P, Rose S, McCreary A. Levodopa infusion does not decrease the onset of abnormal involuntary movements in parkinsonian rats. Mov Disord. 2013;28:1072-9 pubmed publisher
    ..d. infusion does not reduce the risk of the appearance of dyskinesia. By contrast, the duration of established dyskinesia can be reduced by more continuous l-dopa delivery in agreement with clinical experience. ..
  32. Howard C, Pastuzyn E, Barker Haliski M, Garris P, Keefe K. Phasic-like stimulation of the medial forebrain bundle augments striatal gene expression despite methamphetamine-induced partial dopamine denervation. J Neurochem. 2013;125:555-65 pubmed publisher
  33. Bagga V, Dunnett S, Fricker Gates R. Ascorbic acid increases the number of dopamine neurons in vitro and in transplants to the 6-OHDA-lesioned rat brain. Cell Transplant. 2008;17:763-73 pubmed
  34. Wagner A, Sokoloski J, Ren D, Chen X, Khan A, Zafonte R, et al. Controlled cortical impact injury affects dopaminergic transmission in the rat striatum. J Neurochem. 2005;95:457-65 pubmed
    ..with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB)...
  35. Galati S, D Angelo V, Olivola E, Marzetti F, Di Giovanni G, Stanzione P, et al. Acute inactivation of the medial forebrain bundle imposes oscillations in the SNr: a challenge for the 6-OHDA model?. Exp Neurol. 2010;225:294-301 pubmed publisher
    ..Both TTX and 6-OHDA were infused into the medial forebrain bundle (MFB)...
  36. Stone E, Lin Y, Ahsan R, Quartermain D. Role of locus coeruleus alpha1-adrenoceptors in motor activity in rats. Synapse. 2004;54:164-72 pubmed
  37. Kohl S, Baldermann J. Progress and challenges in deep brain stimulation for obsessive-compulsive disorder. Pharmacol Ther. 2018;186:168-175 pubmed publisher
    ..both white matter trajectories (anterior limb of the internal capsule, inferior thalamic peduncle, and medial forebrain bundle) and grey matter subcortical nuclei (nucleus accumbens, nucleus subthalamicus, and bed nucleus of the ..
  38. Ngema P, Mabandla M. Post 6-OHDA lesion exposure to stress affects neurotrophic factor expression and aggravates motor impairment. Metab Brain Dis. 2017;32:1061-1067 pubmed publisher
    ..In this study, the neurotoxin 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle of male Sprague Dawley rats...
  39. Jungnickel J, Kalve I, Reimers L, Nobre A, Wesemann M, Ratzka A, et al. Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats. Behav Brain Res. 2011;216:129-35 pubmed publisher
    ..After unilateral 6-OHDA lesion of the medial forebrain bundle, we observed reduced locomotor activity in the EPM (wall-rearing, entries in closed arms) in lesioned and ..
  40. Mertens B, Massie A, Michotte Y, Sarre S. Effect of nigrostriatal damage induced by 6-hydroxydopamine on the expression of glial cell line-derived neurotrophic factor in the striatum of the rat. Neuroscience. 2009;162:148-54 pubmed publisher
    ..mRNA and protein expression levels of GDNF in the striatum as a function of time following a striatal or medial forebrain bundle 6-hydroxydopamine lesion...
  41. Magill P, Sharott A, Harnack D, Kupsch A, Meissner W, Brown P. Coherent spike-wave oscillations in the cortex and subthalamic nucleus of the freely moving rat. Neuroscience. 2005;132:659-64 pubmed
    ..Finally, these findings also reiterate the importance of oscillations in these circuits in normal behaviour. ..
  42. Nichols N, Cimini M, Haas J, Staton B, Tedroff J, Svensson K. PNU-96391A (OSU6162) antagonizes the development of behavioral sensitization induced by dopamine agonists in a rat model for Parkinson's disease. Neuropharmacology. 2002;43:817-24 pubmed
    ..These results suggest that PNU-96391A could be therapeutically useful to prevent the development of behavioral sensitization induced by DA agonists. ..
  43. McRae Degueurce A, Hjorth S, Dillon D, Mason D, Tice T. Implantable microencapsulated dopamine (DA): a new approach for slow-release DA delivery into brain tissue. Neurosci Lett. 1988;92:303-9 pubmed
    ..This technology has considerable potential for basic and possibly also clinical research. ..
  44. Taylor I, Ilitchev A, Michael A. Restricted diffusion of dopamine in the rat dorsal striatum. ACS Chem Neurosci. 2013;4:870-8 pubmed publisher
    ..We used voltammetry to record dopamine overflow in dorsal striatum while stimulating the medial forebrain bundle over a range of stimulus currents and frequencies...
  45. Sindhu K, Saravanan K, Mohanakumar K. Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed following intranigral or median forebrain bundle infusion. Brain Res. 2005;1051:25-34 pubmed
  46. Ingham C, Hood S, Arbuthnott G. Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res. 1989;503:334-8 pubmed
    ..were studied in the rat neostriatum at various times after a unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At both short (12-26 days) and long (7-12 months) survival times, the density of spines was ..
  47. Chao O, Pum M, Li J, Huston J. The grid-walking test: assessment of sensorimotor deficits after moderate or severe dopamine depletion by 6-hydroxydopamine lesions in the dorsal striatum and medial forebrain bundle. Neuroscience. 2012;202:318-25 pubmed publisher
    ..In Experiment 1, 2 weeks after the injection of 6-OHDA into the medial forebrain bundle, adult Wistar rats were divided into an l-3,4-dihydroxyphenylalanine (L-dopa) and a vehicle treatment ..
  48. Kelley S, Hodge C. The 5-HT3 antagonist Y-25130 blocks cocaine-induced lowering of ICSS reward thresholds in the rat. Pharmacol Biochem Behav. 2003;74:297-302 pubmed
    ..bipolar stimulation electrodes and trained to self-administer electrical stimulation delivered to the medial forebrain bundle-lateral hypothalamus (MFB-LH)...
  49. Henderson J, Doherty K, Allbutt H, Billing R. Effects of pallidotomy on motor symptoms in an animal model of Parkinson's disease. Behav Brain Res. 2006;169:29-38 pubmed
    ..four groups (each of 10 rats) which received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (mfb) plus sham surgery to the pallidum, sham surgery of mfb plus N-methyl-D-aspartate (NMDA) induced ..
  50. Ellison G. Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry. Eur Neuropsychopharmacol. 2002;12:287-97 pubmed
  51. Narang N, Wamsley J. Time dependent changes in DA uptake sites, D1 and D2 receptor binding and mRNA after 6-OHDA lesions of the medial forebrain bundle in the rat brain. J Chem Neuroanat. 1995;9:41-53 pubmed
    ..Animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4, 6, 8, and 16 weeks postlesion...
  52. Gu S, Huang H, Bi J, Yao Y, Wen T. Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model. Brain Res. 2009;1257:1-9 pubmed publisher
    ..rNSCs-NT3 is able to differentiate into dompaminergic neuron in the ventral tegmental area (VTA) and the medial forebrain bundle (MFB), and migrated around the lesion site...
  53. Sari Y, Powrozek T, Zhou F. Alcohol deters the outgrowth of serotonergic neurons at midgestation. J Biomed Sci. 2001;8:119-25 pubmed
    ..neurons in both the median and dorsal raphe, and the amount of 5-HT-immunoreactive fibers in the medial forebrain bundle (MFB). The diameter of the 5-HT-immunoreactive MFB was also reduced as a result of treatment...