Details

Autor(en) / Beteiligte

• Papp, Mariusz
• Gruca, Piotr
• Lason-Tyburkiewicz, Magdalena
• Litwa, Ewa
• Niemczyk, Monika
• Tota-Glowczyk, Katarzyna
• Willner, Paul

Titel

Dopaminergic mechanisms in memory consolidation and antidepressant reversal of a chronic mild stress-induced cognitive impairment

Ist Teil von

• Psychopharmacology, 2017-09, Vol.234 (17), p.2571-2585

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2017

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• Cognitive deficits in depression can be modelled using the novel object recognition (NOR) test, performance in which is impaired by chronic mild stress (CMS). We aimed to examine the involvement of mesocorticolimbic DA terminal regions, and to establish the substrate for CMS-induced impairment of NOR and its reversal by chronic antidepressant treatment. In experiments 1 and 2, we examined the effect of infusions into medial PFC, dorsal hippocampus (HPC), and nucleus accumbens (NAc) shell of D1 and D2 antagonists and D3 agonist, which were predicted to impair NOR with a short (1 h) delay, and of D1 and D2 agonists and D3 antagonist, which were predicted to facilitate NOR with a long (24 h) delay. Using optimal doses identified in experiment 2, in experiments 3 and 4, we examined effects on drug-stimulated NOR of CMS and chronic treatment with venlafaxine (VFX) or risperidone (RSP). We found a wide involvement of DA systems in memory for NOR: D1 receptors in PFC, HPC, and NAc; D3 receptors in PFC and HPC; and D2 receptors in PFC. CMS impaired D2- and D3-mediated effects in PFC and HPC; antidepressants rescued those effects in PFC but not HPC. The involvement of DA in NOR is multifaceted, but the effects of CMS and antidepressants are more discrete, involving D2 and D3 receptors in PFC specifically. While raising many difficult questions, these results suggest that the D2 and D3 receptors in the medial PFC may be an important substrate for cognitive deficits in depression and their remediation.