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- Title
Increased Hippocampal CREB Phosphorylation in Dopamine D3 Receptor Knockout Mice Following Passive Avoidance Conditioning.
- Authors
D’Amico, Agata Grazia; Scuderi, Soraya; Leggio, Gian Marco; Castorina, Alessandro; Drago, Filippo; D’Agata, Velia
- Abstract
Dopamine D 3 receptors (D 3Rs) are implicated in synaptic plasticity and memory processes. Previously we have shown that D 3Rs mediate inhibitory effects on learning, since D 3R knockout (D 3−/−) mice display enhanced performance in the passive avoidance task (PA). Formation of new memories is known to require de novo synthesis of proteins related to synaptic function through the activation of signaling pathways including the mitogen-activated protein kinases (MAPKs) and activation of the nuclear transcription factor cAMP response element binding protein (CREB). However, there are no clear indications regarding the specific involvement of D 3Rs in the activation of these signaling cascades after acquisition of PA. Therefore, in this study we assessed whether phosphorylation levels of several MAPKs, Akt and CREB were differentially affected by PA in both wild-type (WT) and D 3−/− mice hippocampi. Animals were divided in Naïve, unconditioned stimulus trained, conditioned stimulus trained and conditioned animals. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2), c-Jun-N-terminal kinase (JNK) and p38, as well as of Akt and CREB were determined. Acquisition of PA significantly increased pCREB levels both in WT and D 3−/− mice. The extent of PA-driven increase in pCREB levels was significantly higher in mice lacking D 3Rs. Similarly, pERK 1/2 was further augmented in trained D 3−/− mice as compared to trained WTs, whereas JNK and p38 phosphorylation was not affected neither by PA nor by genetic background. Finally, Akt activation was observed in D 3−/− mice, but not in response to PA. In conclusion, these data supports the notion that D 3Rs might modulate CREB phosphorylation after acquisition of PA, probably via activation of ERK signaling.
- Subjects
HIPPOCAMPUS physiology; PHOSPHORYLATION; DOPAMINE receptors; AVOIDANCE conditioning; LABORATORY mice; CREB protein; MEMORY; NEUROPLASTICITY
- Publication
Neurochemical Research, 2013, Vol 38, Issue 12, p2516
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-013-1164-3