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Sucrose consumption test reveals pharmacoresistant depression-associated behavior in two mouse models of temporal lobe epilepsy.

Experimental neurology (2014-09-16)
Sabine Klein, Jens P Bankstahl, Wolfgang Löscher, Marion Bankstahl
ABSTRACT

Among the comorbidities observed in epilepsy patients depression is the most frequent one. Likewise, depression by itself is accompanied by an increased risk to develop epilepsy. Both epilepsy and depression are characterized by a high incidence of pharmacoresistance, which might be based on overactivity of multidrug transporters like P-glycoprotein at the blood-brain barrier. Using genetically modified mice in preclinical epilepsy research is pivotal for investigating this bidirectional relationship. In the present study, we used the sucrose consumption test (SCT) in the pilocarpine and the intrahippocampal kainate mouse post-status epilepticus model to reveal anhedonic behavior, i.e. hyposensitivity to pleasure, as a key symptom of depression. Mice were repetitively investigated by SCT during early epilepsy and the chronic phase of the disease, during which response to antidepressant drug treatment was assessed. SCT revealed long-lasting anhedonia in both models. Anhedonia appeared to be pharmacoresistant, as neither chronic treatment with imipramine in the pilocarpine model nor chronic treatment with fluoxetine in the kainate model could annihilate the differences in sucrose consumption between control and epileptic mice. Moreover, knock-out of P-glycoprotein did not improve the treatment effect of fluoxetine. In conclusion, our findings show for the first time that the SCT is suited for detection of depression-like behavior in mouse models of temporal-lobe epilepsy. Both models might serve as tools to further investigate the neurobiology and pharmacology of epilepsy-associated pharmacoresistant depression.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sucrose, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Sucrose, BioXtra, ≥99.5% (GC)
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Sucrose, ≥99.5% (GC)
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Sucrose, BioUltra, for molecular biology, ≥99.5% (HPLC)
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Sucrose, puriss., meets analytical specification of Ph. Eur., BP, NF
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Sucrose, ≥99.5%
Supelco
Sucrose, Pharmaceutical Secondary Standard; Certified Reference Material
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Sucrose, ACS reagent
Millipore
Sucrose, suitable for microbiology, ACS reagent, ≥99.0%
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Sucrose, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99.5% (GC)
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Fluoxetine hydrochloride, solid
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Chloral hydrate, meets analytical specification of Ph. Eur., BP, USP, 99.5-101%
USP
Sucrose, United States Pharmacopeia (USP) Reference Standard
Supelco
Fluoxetine Hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
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Saccharin, ≥98%
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Pilocarpine hydrochloride, ≥99% (titration), powder
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Sucrose, meets USP testing specifications
Supelco
Sucrose, analytical standard
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Saccharin, ≥99%
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Imipramine hydrochloride, ≥99% (TLC)
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Chloral hydrate, crystallized, ≥98.0% (T)
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Sucrose, Grade II, suitable for plant cell culture
Supelco
Mettler-Toledo Calibration substance ME 51143091, Saccharin, traceable to primary standards (LGC)
Sucrose, European Pharmacopoeia (EP) Reference Standard
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Saccharin, Pharmaceutical Secondary Standard; Certified Reference Material
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Sucrose, Grade I, suitable for plant cell culture
USP
Fluoxetine hydrochloride, United States Pharmacopeia (USP) Reference Standard
Fluoxetine hydrochloride, European Pharmacopoeia (EP) Reference Standard
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Imipramine hydrochloride, BioXtra, ≥99% (TLC)
Supelco
Sucrose, analytical standard, for enzymatic assay kit SCA20