Changes in alfa1-adrenergic receptor subtypes in the hippocampus of rats non-responding to imipramine treatment in the chronic mild stress model of depression

• Autorzy: Rafa-Zablocka K. , Zelek-Molik A. , Bielawski A. , Gruca P. , Lason-Tyburkiewicz M. , Papp M. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

Despite many years of research on depression the mechanism of the disorder remains elusive. Many studies are focused on dysfunction of central monoaminergic systems and some evidence exist for the role of α1-adrenoceptor (α1-AR). There are three subtypes of this receptor - α1A, α1B and α1D, which are widely distributed in brain. The aim of this study was to assess the expression of all three α1-AR, both at the mRNA and at the protein level in the hippocampi of male Wistar rats, subjected to the chronic mild stress (CMS) procedure followed by treatment with antidepressant drug, imipramine (IMI). Five groups of animals were studied: sham-saline; stress-saline; sham-IMI; stress-IMIresponders and stress-IMI-non-responders. The latter included the stressed animals resistant to IMI treatment as indicated by anhedonia test. The mRNA level was measured using qRT-PCR and SybrGreen dye, and the protein level was assessed by Western blotting. We found that mRNA expression of all α1-AR subtypes was significantly elevated only in the IMI-non-responders group (α1A-AR by 76%; α1B-AR by 96%; α1D-AR by 50%, vs. shamsaline). Moreover, stress alone caused an increase in α1A-AR mRNA (by 41%) though the effect was statistically insignificant. Changes found in the protein level were less pronounced. The only difference between IMI-responders and non-responders was found in α1A receptor protein that was decreased by 73% vs IMIresponders. The level of α1D protein was elevated in all IMI treated groups (by about 79%, vs. sham-saline) and the change occurred independently on stress procedure. No change in the α1B protein was found. Our results indicate that although α1A-AR and α1D-AR are involved in mechanism of IMI action, only the α1A receptor seems to be engaged in the phenomenon of resistance to IMI treatment. Supported by a grant POIG.01.01.02-12-004/09-00 financed by European Regional Development Fund.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.47

Twórcy

autor

Rafa-Zablocka K.

• Department of Brain Biochemistry, Institute of Pharmacology PAS, Krakow, Poland

autor

Zelek-Molik A.

• Department of Brain Biochemistry, Institute of Pharmacology PAS, Krakow, Poland

autor

Bielawski A.

• Department of Brain Biochemistry, Institute of Pharmacology PAS, Krakow, Poland

autor

Gruca P.

• Department of Pharmacology, Institute of Pharmacoogy PAS, Krakow, Poland

autor

Lason-Tyburkiewicz M.

• Department of Pharmacology, Institute of Pharmacoogy PAS, Krakow, Poland

autor

Papp M.

• Department of Pharmacology, Institute of Pharmacoogy PAS, Krakow, Poland

autor

Nalepa I.

• Department of Brain Biochemistry, Institute of Pharmacology PAS, Krakow, Poland

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