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Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST).
Eur Neuropsychopharmacol. 2008 Apr; 18(4):271-7.EN

Abstract

Evidence exists for a dopaminergic system dysregulation in mood disorders. In particular, depression may be accompanied by a relative fall of brain dopamine (DA) availability, while the increase of dopamine D2/D3 receptors (D2R/D3R) binding may reflect a compensatory change following primary reduction of mesolimbic DA levels. It is well established that D3Rs, acting as autoreceptors, inhibit DA synthesis and release, although lack of selective compounds have limited the progress in understanding D3Rs role in mood disorders. Aim of this study was to assess the behavioral responses of D3R-deficient (D3(-/-)) mice tested in the forced swim test (FST) and to evaluate their sensitivity to the treatment with different antidepressant drugs. Different groups of mice received one injection of the tricyclic compound, clomipramine (1, 5 and 10 mg/kg) or of one the selective serotonin reuptake inhibitors (SSRIs), paroxetine, sertraline or citalopram (1, 4 and 16 mg/kg), 30 min prior the behavioral test. Vehicle-injected wild type (WT) mice and D3(-/-) animals were used as controls and submitted to the same experimental procedure. In a preliminary experiment, vehicle-injected D3(-/-) mice, but not their littermates, failed to show an increased immobility time in FST as compared to intact controls, suggesting an increased resistance to injection-induced stress in the former. Clomipramine 1 mg/kg failed to affect behavioral responses of both D3(-/-) mice and WT animals. After the 5 mg/kg dose, D3(-/-) and WT mice showed a better performance in FST than vehicle-injected controls, with a lower immobility time exhibited by D3(-/-) mice than that shown by WT animals. No difference was found between WT mice treated with the highest dose of clomipramine (10 mg/kg) and the respective controls, although D3(-/-) mice exhibited a decreased immobility time as compared to vehicle-injected controls. In contrast to WT animals, when treated with 1 mg/kg sertraline and the 4 mg/kg dose of every SSRI D3(-/-) mice exhibited a decreased immobility time in FST in comparison to vehicle-injected controls. Furthermore, 16 mg/kg doses of citalopram, paroxetine or sertraline induced a greater reduction of immobility time in D3(-/-) mice than in WT-treated animals as compared to their respective controls. These data suggest that D3(-/-) mice, as being more resistant to stressful procedure than WT littermates, are more sensitive to antidepressants in FST paradigm than the former. Although the present data do not allow any conclusion on the neurochemical base of this difference, it might be possible that the greater sensitivity to antidepressants depends on a higher DA levels in mesolimbic pathways following the lack of D3Rs.

Authors+Show Affiliations

Department of Experimental and Clinical Pharmacology, University of Catania Medical School, 95125 Catania, Italy.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17804207

Citation

Leggio, Gian Marco, et al. "Increased Sensitivity to Antidepressants of D3 Dopamine Receptor-deficient Mice in the Forced Swim Test (FST)." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 18, no. 4, 2008, pp. 271-7.
Leggio GM, Micale V, Drago F. Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). Eur Neuropsychopharmacol. 2008;18(4):271-7.
Leggio, G. M., Micale, V., & Drago, F. (2008). Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 18(4), 271-7.
Leggio GM, Micale V, Drago F. Increased Sensitivity to Antidepressants of D3 Dopamine Receptor-deficient Mice in the Forced Swim Test (FST). Eur Neuropsychopharmacol. 2008;18(4):271-7. PubMed PMID: 17804207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased sensitivity to antidepressants of D3 dopamine receptor-deficient mice in the forced swim test (FST). AU - Leggio,Gian Marco, AU - Micale,Vincenzo, AU - Drago,Filippo, Y1 - 2007/09/04/ PY - 2006/12/26/received PY - 2007/05/31/revised PY - 2007/07/05/accepted PY - 2007/9/7/pubmed PY - 2008/4/24/medline PY - 2007/9/7/entrez SP - 271 EP - 7 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 18 IS - 4 N2 - Evidence exists for a dopaminergic system dysregulation in mood disorders. In particular, depression may be accompanied by a relative fall of brain dopamine (DA) availability, while the increase of dopamine D2/D3 receptors (D2R/D3R) binding may reflect a compensatory change following primary reduction of mesolimbic DA levels. It is well established that D3Rs, acting as autoreceptors, inhibit DA synthesis and release, although lack of selective compounds have limited the progress in understanding D3Rs role in mood disorders. Aim of this study was to assess the behavioral responses of D3R-deficient (D3(-/-)) mice tested in the forced swim test (FST) and to evaluate their sensitivity to the treatment with different antidepressant drugs. Different groups of mice received one injection of the tricyclic compound, clomipramine (1, 5 and 10 mg/kg) or of one the selective serotonin reuptake inhibitors (SSRIs), paroxetine, sertraline or citalopram (1, 4 and 16 mg/kg), 30 min prior the behavioral test. Vehicle-injected wild type (WT) mice and D3(-/-) animals were used as controls and submitted to the same experimental procedure. In a preliminary experiment, vehicle-injected D3(-/-) mice, but not their littermates, failed to show an increased immobility time in FST as compared to intact controls, suggesting an increased resistance to injection-induced stress in the former. Clomipramine 1 mg/kg failed to affect behavioral responses of both D3(-/-) mice and WT animals. After the 5 mg/kg dose, D3(-/-) and WT mice showed a better performance in FST than vehicle-injected controls, with a lower immobility time exhibited by D3(-/-) mice than that shown by WT animals. No difference was found between WT mice treated with the highest dose of clomipramine (10 mg/kg) and the respective controls, although D3(-/-) mice exhibited a decreased immobility time as compared to vehicle-injected controls. In contrast to WT animals, when treated with 1 mg/kg sertraline and the 4 mg/kg dose of every SSRI D3(-/-) mice exhibited a decreased immobility time in FST in comparison to vehicle-injected controls. Furthermore, 16 mg/kg doses of citalopram, paroxetine or sertraline induced a greater reduction of immobility time in D3(-/-) mice than in WT-treated animals as compared to their respective controls. These data suggest that D3(-/-) mice, as being more resistant to stressful procedure than WT littermates, are more sensitive to antidepressants in FST paradigm than the former. Although the present data do not allow any conclusion on the neurochemical base of this difference, it might be possible that the greater sensitivity to antidepressants depends on a higher DA levels in mesolimbic pathways following the lack of D3Rs. SN - 0924-977X UR - https://www.unboundmedicine.com/medline/citation/17804207/Increased_sensitivity_to_antidepressants_of_D3_dopamine_receptor_deficient_mice_in_the_forced_swim_test__FST__ DB - PRIME DP - Unbound Medicine ER -