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Antidepressant-like activity of the adenosine A(2A) receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents.
Pharmacol Biochem Behav. 2013 Dec; 114-115:23-30.PB

Abstract

RATIONALE

Depression is common in Parkinson's disease (PD) but its response to classical antidepressants is not clear. The adenosine A2A antagonist istradefylline is effective in the treatment of the motor symptoms of PD but inhibition of the adenosine A2A receptor may also induce antidepressant-like effects.

OBJECTIVE

We have investigated whether istradefylline might be effective in treating depression in PD using the forced swimming test (FST) and the tail suspension test (TST) in rodents.

RESULTS

Istradefylline significantly decreased immobility time in the FST in both rats and mice (0.16mg/kg and higher) with comparable efficacy to an equivalent dose of the tricyclic antidepressants, desipramine and imipramine. Both 8-OH-DPAT (5-HT1A agonist) and quinpirole (D2 agonist) also reduced the immobility time. The istradefylline-induced reduction of immobility time was attenuated by corticosterone. In addition, the combined use of a sub-threshold dose of istradefylline and the serotonin-noradrenaline reuptake inhibitor venlafaxine ameliorated depression-like behavior in the mouse FST. In the mouse TST, istradefylline (0.08mg/kg and higher) decreased immobility time. Moreover, co-administration of istradefylline with paroxetine or fluoxetine (selective serotonin reuptake inhibitors) or deprenyl (MAO-B inhibitor) at doses that did not show antidepressant-like effects when administered alone, resulted in a significant reduction in immobility time.

CONCLUSIONS

Istradefylline alone or co-administered with currently available antidepressants, may be useful for the treatment of depression as well as motor symptoms of PD. Its effects might be, at least in part, attributable to modulation of hypothalamic-pituitary-adrenal axis.

Authors+Show Affiliations

Development Research Laboratories, Research Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24201052

Citation

Yamada, Koji, et al. "Antidepressant-like Activity of the Adenosine A(2A) Receptor Antagonist, Istradefylline (KW-6002), in the Forced Swim Test and the Tail Suspension Test in Rodents." Pharmacology, Biochemistry, and Behavior, vol. 114-115, 2013, pp. 23-30.
Yamada K, Kobayashi M, Mori A, et al. Antidepressant-like activity of the adenosine A(2A) receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents. Pharmacol Biochem Behav. 2013;114-115:23-30.
Yamada, K., Kobayashi, M., Mori, A., Jenner, P., & Kanda, T. (2013). Antidepressant-like activity of the adenosine A(2A) receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents. Pharmacology, Biochemistry, and Behavior, 114-115, 23-30. https://doi.org/10.1016/j.pbb.2013.10.022
Yamada K, et al. Antidepressant-like Activity of the Adenosine A(2A) Receptor Antagonist, Istradefylline (KW-6002), in the Forced Swim Test and the Tail Suspension Test in Rodents. Pharmacol Biochem Behav. 2013;114-115:23-30. PubMed PMID: 24201052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like activity of the adenosine A(2A) receptor antagonist, istradefylline (KW-6002), in the forced swim test and the tail suspension test in rodents. AU - Yamada,Koji, AU - Kobayashi,Minoru, AU - Mori,Akihisa, AU - Jenner,Peter, AU - Kanda,Tomoyuki, Y1 - 2013/11/04/ PY - 2013/08/19/received PY - 2013/10/15/revised PY - 2013/10/23/accepted PY - 2013/11/9/entrez PY - 2013/11/10/pubmed PY - 2014/7/23/medline KW - 5-HT KW - 5-hydroxytryptamine KW - 50% effective dose KW - 8-OH-DPAT KW - 8-hydroxy-2-(dipropylamino)tetralin KW - ACTH KW - Adenosine A(2A) receptor KW - Antidepressant KW - COMT KW - ED(50) KW - FST KW - Forced swimming test KW - HPA KW - Istradefylline KW - KW-6002 KW - MAO KW - MED KW - PD KW - Parkinson's disease KW - SNRI KW - SSRI KW - TCA KW - TST KW - Tail suspension test KW - adrenocorticotropic hormone KW - catecholamine-O-methyltransferase KW - forced swim test KW - hypothalamic–pituitary–adrenal KW - minimum effective dose KW - monoamine oxidase KW - serotonin noradrenaline reuptake inhibitor KW - serotonin-noradrenaline reuptake inhibitor KW - tail suspension test KW - tricyclic antidepressant SP - 23 EP - 30 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 114-115 N2 - RATIONALE: Depression is common in Parkinson's disease (PD) but its response to classical antidepressants is not clear. The adenosine A2A antagonist istradefylline is effective in the treatment of the motor symptoms of PD but inhibition of the adenosine A2A receptor may also induce antidepressant-like effects. OBJECTIVE: We have investigated whether istradefylline might be effective in treating depression in PD using the forced swimming test (FST) and the tail suspension test (TST) in rodents. RESULTS: Istradefylline significantly decreased immobility time in the FST in both rats and mice (0.16mg/kg and higher) with comparable efficacy to an equivalent dose of the tricyclic antidepressants, desipramine and imipramine. Both 8-OH-DPAT (5-HT1A agonist) and quinpirole (D2 agonist) also reduced the immobility time. The istradefylline-induced reduction of immobility time was attenuated by corticosterone. In addition, the combined use of a sub-threshold dose of istradefylline and the serotonin-noradrenaline reuptake inhibitor venlafaxine ameliorated depression-like behavior in the mouse FST. In the mouse TST, istradefylline (0.08mg/kg and higher) decreased immobility time. Moreover, co-administration of istradefylline with paroxetine or fluoxetine (selective serotonin reuptake inhibitors) or deprenyl (MAO-B inhibitor) at doses that did not show antidepressant-like effects when administered alone, resulted in a significant reduction in immobility time. CONCLUSIONS: Istradefylline alone or co-administered with currently available antidepressants, may be useful for the treatment of depression as well as motor symptoms of PD. Its effects might be, at least in part, attributable to modulation of hypothalamic-pituitary-adrenal axis. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/24201052/Antidepressant_like_activity_of_the_adenosine_A_2A__receptor_antagonist_istradefylline__KW_6002__in_the_forced_swim_test_and_the_tail_suspension_test_in_rodents_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(13)00268-2 DB - PRIME DP - Unbound Medicine ER -