Component

Mouse wake duration

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.

    Mouse dopamine D2 receptor / Drd2 → Mouse wake duration Recorded from sourceungraded
    Experimental context and source evidence
    evidence_access
    Primary indexed abstract checked; full methods and figures not comprehensively reviewed.
    experimental_condition
    Wild-type modafinil exposure drug exposure · Modafinil Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_condition
    Wild-type modafinil exposure deletion · Mouse dopamine D2 receptor / Drd2 Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_contrast
    {"intervention": "D2 deletion during modafinil exposure", "comparator": "Wild-type modafinil exposure", "endpoint": "D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "mouse-drd2", "state": "deletion"}, {"entity_slug": "modafinil", "state": "drug exposure"}]} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Mouse receptor knockout and pharmacology; antagonist effects varied with modafinil dose.
    interpretation_status
    Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
    limitations
    Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
    plain_language
    D2 receptor deletion reduced modafinil-induced wakefulness in mice; D1-like antagonist addition abolished the residual response.
    primary_references
    Dopaminergic D1 and D2 receptors are essential for the arousal effect of modafinil. | 2008 | DOI 10.1523/jneurosci.1819-08.2008 | PMID 18716204 | https://pubmed.ncbi.nlm.nih.gov/18716204/
    source_locator
    Reviewed reference lines 73-73; exact primary location described in quoted passage where extracted.

    Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 73–73

    Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse receptor knockout and pharmacology; antagonist effects varied with modafinil dose. · Recorded from source · Recorded from source

    In mice, D2-receptor deletion reduced modafinil-induced wakefulness. Adding a D1-like antagonist abolished the remaining response. In wild-type mice, antagonist effects depended on modafinil dose. This supports dopamine-receptor involvement, not one fixed D1/D2 contribution across exposures. Pharmacological receptor-family blockade should not automatically become proof of a unique receptor subtype or anatomical location. [Qu et al., 2008](https://pubmed.ncbi.nlm.nih.gov/18716204/)
    Complete structured claim and evidence

  2. DAT knockout abolished the usual modafinil wake-promoting response in mice while caffeine remained effective with enhanced response.

    Mouse dopamine transporter / Slc6a3 → Mouse wake duration Recorded from sourceungraded
    Experimental context and source evidence
    evidence_access
    Primary indexed abstract checked; full methods and figures not comprehensively reviewed.
    experimental_condition
    Modafinil in wild-type mice drug challenge · Modafinil Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_condition
    Modafinil in wild-type mice knockout · Mouse dopamine transporter / Slc6a3 Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_contrast
    {"intervention": "Modafinil in DAT-knockout mice", "comparator": "Modafinil in wild-type mice", "endpoint": "DAT knockout abolished the usual modafinil wake-promoting response in mice while caffeine remained effective with enhanced response.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "mouse-slc6a3", "state": "knockout"}, {"entity_slug": "modafinil", "state": "drug challenge"}]} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Constitutive mouse DAT knockout; baseline and developmental compensation constrain interpretation.
    interpretation_status
    Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
    limitations
    Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
    plain_language
    DAT knockout abolished the usual modafinil wake-promoting response in mice while caffeine remained effective with enhanced response.
    primary_references
    Dopaminergic role in stimulant-induced wakefulness. | 2001 | DOI 10.1523/jneurosci.21-05-01787.2001 | PMID 11222668 | https://pubmed.ncbi.nlm.nih.gov/11222668/
    source_locator
    Reviewed reference lines 50-50; exact primary location described in quoted passage where extracted.

    Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 50–50

    Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Constitutive mouse DAT knockout; baseline and developmental compensation constrain interpretation. · Recorded from source · Recorded from source

    In DAT-knockout mice, modafinil lost its usual wake-promoting effect; caffeine remained effective and produced an enhanced response. This supports a DAT-dependent route in that model, rather than a general inability of those mice to awaken. Developmental compensation and changed baseline physiology still limit extrapolation from a constitutive knockout. [Wisor et al., 2001](https://pubmed.ncbi.nlm.nih.gov/11222668/)
    Complete structured claim and evidence

  3. Histamine-neuron ablation or acute chemogenetic inhibition shortened, but did not abolish, modafinil-induced wakefulness in mice.

    Mouse histamine-producing neurons → Mouse wake duration Recorded from sourceungraded
    Experimental context and source evidence
    evidence_access
    Full XML obtained; relevant results/methods inspected. Not exhaustive reanalysis of figures or data.
    experimental_condition
    Modafinil with intact neurons ablated or inhibited · Mouse histamine-producing neurons Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_condition
    Modafinil with intact neurons drug challenge · Modafinil Condition belongs to the full experimental contrast; do not separate a joint intervention.
    experimental_contrast
    {"intervention": "Histamine-neuron ablation/inhibition plus modafinil", "comparator": "Modafinil with intact neurons", "endpoint": "Histamine-neuron ablation or acute chemogenetic inhibition shortened, but did not abolish, modafinil-induced wakefulness in mice.", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "mouse-histamine-neurons", "state": "ablated or inhibited"}, {"entity_slug": "modafinil", "state": "drug challenge"}]} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Mouse genetic and chemogenetic experiments; cell dependency not direct drug binding.
    interpretation_status
    Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
    limitations
    Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
    plain_language
    Histamine-neuron ablation or acute chemogenetic inhibition shortened, but did not abolish, modafinil-induced wakefulness in mice.
    primary_references
    Genetic lesioning of histamine neurons increases sleep-wake fragmentation and reveals their contribution to modafinil-induced wakefulness. | 2019 | DOI 10.1093/sleep/zsz031 | PMID 30722053 | https://pmc.ncbi.nlm.nih.gov/articles/PMC6519916/
    source_locator
    Reviewed reference lines 79-79; exact primary location described in quoted passage where extracted.

    Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 79–79

    Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse genetic and chemogenetic experiments; cell dependency not direct drug binding. · Recorded from source · Recorded from source

    Genetic removal or acute chemogenetic inhibition of histamine neurons shortened modafinil-induced waking in mice rather than abolishing it. Histamine-neuron activity therefore contributes to sustained wakefulness in that setting, without being established as the direct drug target. Recovery sleep still showed increased NREM delta power, including after histamine-neuron ablation: a homeostatic response persisted. [Histamine-neuron study, 2019](https://pmc.ncbi.nlm.nih.gov/articles/PMC6519916/)
    Complete structured claim and evidence

  4. DSP-4 removal of forebrain noradrenergic projections did not eliminate modafinil wake promotion, while an adrenergic antagonist still suppressed it.

    Mouse forebrain noradrenergic projections → Mouse wake duration Recorded from sourceungraded
    Experimental context and source evidence
    evidence_access
    Primary indexed abstract checked; full methods and figures not comprehensively reviewed.
    experimental_contrast
    {"intervention": "Noradrenergic projection lesion plus modafinil", "comparator": "Modafinil without lesion", "endpoint": "DSP-4 removal of forebrain noradrenergic projections did not eliminate modafinil wake promotion, while an adrenergic antagonist still suppressed it.", "effect_direction": "no_detected_change", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Mouse pharmacological lesion experiment; adrenergic involvement does not require a simple obligatory projection relay.
    interpretation_status
    Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
    limitations
    Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
    plain_language
    DSP-4 removal of forebrain noradrenergic projections did not eliminate modafinil wake promotion, while an adrenergic antagonist still suppressed it.
    primary_references
    Dopaminergic-adrenergic interactions in the wake promoting mechanism of modafinil. | 2005 | DOI 10.1016/j.neuroscience.2005.02.003 | PMID 15857707 | https://pubmed.ncbi.nlm.nih.gov/15857707/
    source_locator
    Reviewed reference lines 87-87; exact primary location described in quoted passage where extracted.

    Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 87–87

    Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Mouse pharmacological lesion experiment; adrenergic involvement does not require a simple obligatory projection relay. · Recorded from source · Recorded from source

    In mice, removing forebrain noradrenergic projections with DSP-4 did not eliminate wake promotion, whereas an adrenergic antagonist still suppressed it. The interpretation involved dopamine–adrenergic interactions; the result prevents treating an intact locus-coeruleus projection as an obligatory relay. [2005 intervention study](https://pubmed.ncbi.nlm.nih.gov/15857707/)
    Complete structured claim and evidence

  5. Orexin-null mice retained and in one experiment showed greater wake prolongation after modafinil.

    Modafinil → Mouse wake duration Recorded from sourceungraded
    Experimental context and source evidence
    evidence_access
    Primary indexed abstract checked; full methods and figures not comprehensively reviewed.
    experimental_contrast
    {"intervention": "Modafinil in orexin-null mice", "comparator": "Matched control and wild-type response", "endpoint": "Orexin-null mice retained and in one experiment showed greater wake prolongation after modafinil.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.
    experimental_model
    Orexin-null versus wild-type mice; genetic loss not dietary deficit.
    interpretation_status
    Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.
    limitations
    Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.
    plain_language
    Orexin-null mice retained and in one experiment showed greater wake prolongation after modafinil.
    primary_references
    Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. | 2005 | DOI 10.1016/j.neuroscience.2004.10.005 | PMID 15652995 | https://pubmed.ncbi.nlm.nih.gov/15652995/
    source_locator
    Reviewed reference lines 81-81; exact primary location described in quoted passage where extracted.

    Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 81–81

    Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Orexin-null versus wild-type mice; genetic loss not dietary deficit. · Recorded from source · Recorded from source

    Orexin-null mice retained—and in one experiment showed greater—wake prolongation after modafinil. However, direct wake-to-REM transitions were not suppressed, and an EEG correlate of alertness was only partly restored. Thus, **wake duration, cataplexy-related phenomena and quality of alertness are separable**. An intact orexin system was unnecessary for one endpoint, not irrelevant to every endpoint. [Orexin-null experiment](https://pubmed.ncbi.nlm.nih.gov/15652995/)
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.