Introduction: Drugs of abuse usurp learning and memory mechanisms normally related to neuronal rewards producing long-lasting neuroadaptation that underlies drug-seeking behavior and relapse. These alterations involve NMDA-dependent long-term plasticity in neural structure related to addiction such as the nucleus accumbens (NAc). Objectives: Aim of the present study was to investigate whether D-serine, released by astrocytes and/or neurons, may be involved in regulating synaptic activity and plasticity in the NAc. Methods: Experiments have been performed by using electrophysiological and immunohistochemical techniques. Coronal brain slices containing the NAc were prepared from Wistar rats (28 days old). Results: Pre-incubation of slices with D-amino acid oxidase (DAAO; 0.2 U/mL), a D-serine degrading enzyme, induced a significant increase of the AMPA/NMDA ratio at prefrontal cortex-medium spiny neuron synapses (from 1.3±0.2 to 5.8±1.5). This result suggests that D-serine modulates the NMDA component of the EPSCs. Therefore we tested the hypothesis that this amino acid may contribute to the NMDAdependent synaptic plasticity in the NAc. LTP and LTD induction requires the activation of NMDARs; as expected perfusion of the slices with D-AP5, a NMDAR antagonist, abolished these forms of synaptic plasticity. We then compared the amplitude of LTP and LTD in control and in DAAO-treated slices. The results of this set of experiments showed that D-serine degradation strongly reduced LTP and LTD (90.4% and 99.2%, respectively) thus indicating that this amino acid is required for these forms of plasticity. As for the cellular origin of D-serine, preliminary results from immunohistochemical experiments suggest a prevalent astrocytic site of production. Conclusions: These data suggest that astrocytic D-serine regulates NMDARs function and synaptic plasticity in the NAc. Ongoing experiments will address whether this signaling is impaired in cocaine model of drug addiction.
|Numero di pagine
|Stato di pubblicazione
|Pubblicato - 2011
|14th European Congress on Clinical Neurophysiology - Roma
Durata: 21 giu 2011 → 24 giu 2011
- Synaptic plasticity