Antidepressant-like effect of pramipexole in an inflammatory model of depression.
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.
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Vicente
V
Lieberknecht
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Mauricio Peña
MP
Cunha
Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Stella Célio
SC
Junqueira
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Igor Dos Santos
ID
Coelho
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Luiz Felipe
LF
de Souza
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Adair Roberto Soares
AR
Dos Santos
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Ana Lúcia S
AL
Rodrigues
Laboratory of Autoimmunity and Immunopharmacology, Campus Araranguá, Federal University of Santa Catarina, 88906-072, Araranguá, SC, Brazil.
Rafael Cypriano
RC
Dutra
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil. Electronic address: alcir.dafre@ufsc.br.
Alcir Luiz
AL
Dafre
D000818:Animals; D052160:Benzothiazoles / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000627:therapeutic use*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055809:Illness Behavior / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D000077487:Pramipexole; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D052160:Benzothiazoles; D018491:Dopamine Agonists; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D000077487:Pramipexole
Dopamine receptor; Lipopolysaccharide; Mood disorders; Neuroinflammation; Pramipexole