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Antidepressant-like effect of pramipexole in an inflammatory model of depression.

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      Abstract

      Pramipexole (PPX), a dopamine D2/3 receptor preferring agonist, is currently in use for the treatment of Parkinson's disease symptoms and restless legs syndrome. Recently, anti-inflammatory properties of PPX have been shown in an autoimmune model of multiple sclerosis, and case reports indicate PPX ameliorates depressive symptoms. Since peripheral inflammation is known to induce depression-like behavior in rodents, we assessed the potential antidepressant effect of PPX in an inflammatory model of depression induced by LPS. Repeated (daily for 7days, 1mg/kg, i.p.), but not acute (1h before LPS) treatment with PPX abolished the depression-like behavior induced by LPS (0.1mg/kg, i.p.) in the forced swim test, and the anhedonic behavior in the splash test. Interestingly, PPX per se decreased interleukin 1β levels and reversed LPS-induced increase in its content in mice hippocampus⋅ Repeated PPX treatment also prevented the increase in hippocampal levels of the 3-nitrotyrosine protein adducts induced by LPS. Haloperidol (0.2mg/kg, i.p.) and sulpiride (50mg/kg, i.p.) were unable to prevent the antidepressant-like effect of PPX in LPS-treated mice. Altogether, these results suggest that the observed antidepressant-like effect of PPX in LPS-treated mice may be dependent on its anti-inflammatory properties and may not be related to dopamine D2 receptor activation.

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      Affiliations
      [1 ] Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
      [2 ] Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
      [3 ] Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
      [4 ] Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Federal University of Santa Catarina, 88906-072, Araranguá, SC, Brazil.
      [5 ] Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil. Electronic address: alcir.dafre@ufsc.br.
      Journal
      Behav. Brain Res.
      Behavioural brain research
      Elsevier BV
      1872-7549
      0166-4328
      March 01 2017
      : 320
      27825895
      S0166-4328(16)31010-5
      10.1016/j.bbr.2016.11.007

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