TABLE 3.
Animal studies reporting an association between absence seizures and depression or anxiety along with interventions
| Article | Year of publication | Model | Behavioral tests | Intervention | Administration | Effect of intervention on seizures | Effect of intervention on behavioral disorders |
|---|---|---|---|---|---|---|---|
| Sarkisova et al.37 | 2003 | WAG/Rij | Forced swim, sucrose consumption, open field, light-dark choice, elevated plus maze | Imipramine | Subchronic (15 days) | NA | ↓ depressive behavior; no effect on anxious behavior |
| Sarkisova et al.32 | 2008 | WAG/Rij | Forced swim, sucrose consumption, sucrose preference, open field, light-dark choice | Imipramine, parlodel | Subchronic (15 days) | NA | ↓ depressive behavior; no effect on anxious behavior |
| Shaw et al.52 | 2009 | Long-Evans | Forced swim, sucrose consumption, elevated plus maze, open field | Ethosuximide | Acute | ↓ number of seizures | ↓ depressive behavior; no effect on anxious behavior |
| Sarkisova et al.13 | 2010 | WAG/Rij | Forced swim, sucrose consumption, sucrose preference, light-dark choice, open field | Ethosuximide | Early chronic (P21, 17 days), prolonged early chronic (P21, 152 days) |
↓ number of SWDs | ↓ depressive behavior; no effect on anxious behavior |
| Russo et al.41 | 2011 | WAG/Rij | Forced swim | Carbamazepine, ethosuximide, levetiracetam, zonisamide | Early chronic (P30, 119 days) | ↓ development of seizures and sharp-wave discharges with ethosuximide, levetiracetam, and zonisamide; no effect with carbamazepine | ↓ depressive behavior with ethosuximide; ↑ depressive behavior with levetiracetam; no effect with carbamazepine and zonisamide |
| Russo et al.42 | 2011 | WAG/Rij | Forced swim | Vigabatrin | Subchronic (5 days), early chronic (P30, 119 days) | ↑ number of seizures with subchronic; ↓ number of seizures with early chronic | ↓ depressive behavior |
| Huang et al.15 | 2012 | Long-Evans | Forced swim, sucrose consumption, sucrose preference, elevated plus maze, open field | Lamotrigine | Chronic (35 days) | ↓ number and duration of SWDs | ↓ depressive behavior and anxious behavior |
| Kovacs et al.34 | 2012 | WAG/Rij | Sucrose preference | Clomipramine | Early subchronic (<P21, 14 days) | ↓ sharp-wave discharge activity | ↑ depressive behavior |
| Russo et al.43 | 2013 | WAG/Rij | Forced swim, sucrose preference, elevated plus maze, open field | Aripiprazole | Subchronic (>14 days) | ↓ number and duration of SWDs | ↓ depressive and anxious behavior |
| Russo et al.44 | 2013 | WAG/Rij | Forced swim, sucrose preference | Rapamycin | Acute, subchronic (7 days), early chronic (P45, 119 days) | ↓ number and duration of seizures; ↓ seizure development with early chronic | ↓ depressive behavior with subchronic; ↑ depressive behavior with early chronic; no effect with acute |
| van Luijtelaar et al.40 | 2013 | WAG/Rij | Forced swim, sucrose preference | Ethosuximide | Two months treatment and 4 months treatment | ↓ development of SWDs | ↓ immobility score on forced swim test and no effect on sucrose preference |
| Citraro et al.30 | 2014 | WAG/Rij | Forced swim, open field | Statins | Acute, chronic (119 days), early chronic (<P45, 119 days) | ↓ development of seizures with early chronic; no effect with acute or chronic | ↓ depressive and anxious behavior with early chronic; no effect with acute or chronic |
| Russo et al.46 | 2014 | WAG/Rij | Forced swim | Lipopolysaccharide | Acute | ↑ number and duration of seizures | ↑ depressive behavior |
| Citraro et al.33 | 2015 | WAG/Rij | Forced swim | Haloperidol, risperidone, quetiapine, fluoxetine, duloxetine | Subchronic (49 days), chronic (119 days), early chronic (<P45, 119 days) | ↑ seizure incidence with chronic haloperidol and risperidone; no effect on seizure incidence with chronic quetiapine; no effect on seizure development with early chronic haloperidol, risperidone, or quetiapine; ↓ incidence of nonestablished seizures with early chronic fluoxetine and duloxetine; ↓ incidence of established seizures with chronic duloxetine | ↑ depressive behavior with early chronic haloperidol and risperidone; no effect with quetiapine and duloxetine; ↓ depressive behavior with early chronic fluoxetine |
| Ari et al.31 | 2016 | WAG/Rij | Elevated plus maze | Ketone supplements | Subchronic (7 days), chronic (83 days) | NA | ↓ anxious behavior |
| Citraro et al.47 | 2017 | WAG/Rij | Forced swim, sucrose preference, open field | Perampanel | Acute, subchronic (7 days), early chronic (<P30, 152 days) | No effect with acute and subchronic; ↓ seizure development with chronic | ↓ depressive behavior with early chronic; no effect on anxious behavior |
| Moyanova et al.49 | 2018 | WAG/Rij | Sucrose preference, forced swim | Melatonin | Acute, subchronic (18 days) | No effect on incidence or circadian rhythm of seizures | ↓ depressive behavior with subchronic |
| Sarkisova & Gabova50 | 2018 | WAG/Rij | Forced swim | Maternal care | Prolonged early chronic (>212 days) | ↓ number and duration of seizures | ↓ depressive behavior |
| Leo et al.35 | 2019 | WAG/Rij | Forced swim | Ethosuximide | Chronic (17 days) | NA | ↓ depressive behavior |
| Aygun36 | 2020 | WAG/Rij | forced swim, open field | trazodone | Acute | ↑ number and duration of SWDs | ↑ depressive and anxious behavior |
| Citraro et al.48 | 2020 | WAG/Rij | Forced swim, elevated plus maze | Valproic acid, sodium butyrate | Early chronic (P30, 152 days), prolonged early chronic (P30, 212 days) | ↓ number and duration of SWDs | ↓ depressive behavior with early chronic; ↓ depressive behavior with prolonged early chronic combined administration only; no effect on anxious behavior |
| Dezsi et al.8 | 2013 | GAERS | Open field | Ethosuximide | Early chronic (P21, 154 days) | ↓ frequency of seizures | ↓ anxious behavior |
| Dezsi et al.56 | 2016 | GAERS | Open field, elevated plus maze, light-dark box | Enriched vs. standard environment | Chronic (42 days), early chronic (P21, 77 days) prolonged early chronic (P30, 140 days) | ↓ development and frequency of seizures | ↓ anxious behavior |
| Marks et al.55 | 2019 | GAERS | Open field locomotion, elevated plus maze | Z944, pan-T-type calcium channel antagonist | Acute | NA | ↑ anxious behavior |
Note: Imipramine: antidepressant; parlodel, dopamine agonist; ethosuximide, antiepileptic; carbamazepine: antiepileptic; levetiracetam: antiepileptic; zonisamide: antiepileptic; vigabatrin: antiepileptic; lamotrigine: antiepileptic; clomipramine: antidepressant; aripiprazole: antipsychotic; rapamycin: mammalian target of rapamycin inhibitor; statins: cholesterol synthesis inhibitor; haloperidol: antipsychotic; risperidone: antipsychotic; quetiapine: antipsychotic; fluoxetine: antidepressant; perampanel: antiepileptic; trazodone: antidepressant; valproic acid: antiepileptic.
Abbreviations: GAERS, Genetic Absence Epilepsy From Strasbourg; NA, not available; P, postnatal day; SWD, spike-and-wave discharge; WAG/Rij, Wistar Albino Glaxo From Rijswijk.