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Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors.
Behav Pharmacol. 2006 Nov; 17(7):559-72.BP

Abstract

The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of Parkinson's disease. As it appears to improve mood, we examined its actions in rodent models of antidepressant properties, in comparison with the prototypical anti-Parkinson agent, apomorphine, the D2/D3 receptor agonist, quinpirole, and the antidepressants, imipramine and fluvoxamine. In the mouse forced-swim test, acute administration of imipramine, fluvoxamine, apomorphine or quinpirole decreased immobility time, actions dose dependently mimicked by piribedil (2.5-10.0 mg/kg, subcutaneously). In rats, acute and subchronic administration of piribedil similarly reduced immobility (0.63-10.0 mg/kg, subcutaneously) and apomorphine, quinpirole and imipramine were also active in this test, whereas fluvoxamine was inactive. Both in mice and in rats, the D2/D3 receptor antagonist, raclopride, and the D2 receptor antagonist, L741,626, dose dependently blocked the antidepressant properties of piribedil, whereas the selective D3 receptor antagonists, S33084 and SB277,011, were ineffective. In a chronic mild stress model in rats, piribedil (2.5-40.0 mg/kg, subcutaneously) restored sucrose intake in stressed animals exerting its actions more rapidly (by week 1) than imipramine. Imipramine, fluvoxamine, apomorphine, quinpirole and piribedil dose dependently (0.63-10.0 mg/kg, subcutaneously) suppressed aggressive and marble-burying behaviour in mice. In the latter procedure, raclopride and L741,626, but not S33084, attenuated the actions of piribedil. Over a dose range (0.63-10.0 mg/kg, subcutaneously) equivalent to those active in models of antidepressant activity, piribedil did not stimulate locomotor behaviour. In conclusion, principally via recruitment of D2 receptors, piribedil exerts robust and specific antidepressant-like actions in diverse rodent models.

Authors+Show Affiliations

Psychopharmacology Department, Servier Research Institute, Croissy Research Center, Paris, France. mauricette.brocco@fr.netgrs.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17021388

Citation

Brocco, Mauricette, et al. "Antidepressant-like Properties of the anti-Parkinson Agent, Piribedil, in Rodents: Mediation By Dopamine D2 Receptors." Behavioural Pharmacology, vol. 17, no. 7, 2006, pp. 559-72.
Brocco M, Dekeyne A, Papp M, et al. Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. Behav Pharmacol. 2006;17(7):559-72.
Brocco, M., Dekeyne, A., Papp, M., & Millan, M. J. (2006). Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. Behavioural Pharmacology, 17(7), 559-72.
Brocco M, et al. Antidepressant-like Properties of the anti-Parkinson Agent, Piribedil, in Rodents: Mediation By Dopamine D2 Receptors. Behav Pharmacol. 2006;17(7):559-72. PubMed PMID: 17021388.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant-like properties of the anti-Parkinson agent, piribedil, in rodents: mediation by dopamine D2 receptors. AU - Brocco,Mauricette, AU - Dekeyne,Anne, AU - Papp,Mariusz, AU - Millan,Mark J, PY - 2006/10/6/pubmed PY - 2006/12/9/medline PY - 2006/10/6/entrez SP - 559 EP - 72 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 17 IS - 7 N2 - The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of Parkinson's disease. As it appears to improve mood, we examined its actions in rodent models of antidepressant properties, in comparison with the prototypical anti-Parkinson agent, apomorphine, the D2/D3 receptor agonist, quinpirole, and the antidepressants, imipramine and fluvoxamine. In the mouse forced-swim test, acute administration of imipramine, fluvoxamine, apomorphine or quinpirole decreased immobility time, actions dose dependently mimicked by piribedil (2.5-10.0 mg/kg, subcutaneously). In rats, acute and subchronic administration of piribedil similarly reduced immobility (0.63-10.0 mg/kg, subcutaneously) and apomorphine, quinpirole and imipramine were also active in this test, whereas fluvoxamine was inactive. Both in mice and in rats, the D2/D3 receptor antagonist, raclopride, and the D2 receptor antagonist, L741,626, dose dependently blocked the antidepressant properties of piribedil, whereas the selective D3 receptor antagonists, S33084 and SB277,011, were ineffective. In a chronic mild stress model in rats, piribedil (2.5-40.0 mg/kg, subcutaneously) restored sucrose intake in stressed animals exerting its actions more rapidly (by week 1) than imipramine. Imipramine, fluvoxamine, apomorphine, quinpirole and piribedil dose dependently (0.63-10.0 mg/kg, subcutaneously) suppressed aggressive and marble-burying behaviour in mice. In the latter procedure, raclopride and L741,626, but not S33084, attenuated the actions of piribedil. Over a dose range (0.63-10.0 mg/kg, subcutaneously) equivalent to those active in models of antidepressant activity, piribedil did not stimulate locomotor behaviour. In conclusion, principally via recruitment of D2 receptors, piribedil exerts robust and specific antidepressant-like actions in diverse rodent models. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/17021388/Antidepressant_like_properties_of_the_anti_Parkinson_agent_piribedil_in_rodents:_mediation_by_dopamine_D2_receptors_ L2 - http://dx.doi.org/10.1097/01.fbp.0000236267.41806.5b DB - PRIME DP - Unbound Medicine ER -