Effect of chronic mild stress and prolonged treatment with imipramine on the levels of endogenous Met-enkephalin in the rat dopaminergic mesolimbic system.
Chronic mild stress (CMS)-an established behavioral model of anhedonia, which is one of the core symptoms of major depression-significantly decreases the level of endogenous Met-enkephalin in the rat nucleus accumbens (NAS). Prolonged administration of imipramine (IMI)-the most often used antidepressant drug-increases the level of this peptide in the NAS and reverses the effect of CMS, when administered simultaneously to the animals subjected to CMS. Prolonged administration of IMI decreases the level of Met-enkephalin in the ventral tegmental area (VTA) both in control rats as well as in rats subjected to CMS. Since the endogenous enkephalins have been demonstrated to influence the activity of dopaminergic projection from the VTA to the NAS, the obtained results are discussed in the light of the data pointing to the involvement of mesolimbic dopamine system both in the CMS-induced anhedonia and in the mechanism of therapeutic effect of IMI.
Dziedzicka-Wasylewska
M
M
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Papp
M
M
D000818:Animals; D003863:Depression / Q000378:metabolism / Q000503:physiopathology; D004744:Enkephalin, Methionine / Q000032:analysis* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D008032:Limbic System / Q000737:chemistry* / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
D004744:Enkephalin, Methionine; D007099:Imipramine