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Titolo: Changes in CB1R expression and function in PFC of rats exposed to food restriction paradigm
Data di pubblicazione: 2012
Abstract: Endocannabinoid (eCB) system is involved in the regulation of appetite and food intake behavior both in animals and humans. CB type-1 receptors (CB1Rs) are expressed at a high level in hippocampus, BLA and prefrontal cortex (PFC), an area that plays a key role in working memory and reward. Principal dopaminergic (DA) afferences from the VTA are crucial for PFC functions and recent evidence suggests that D2Rs and CB1Rs are co-expressed on GABAergic terminals in PFC. In order to elucidate the role of CB1Rs in the regulation of DA release in PFC during feeding phases we exposed the rats to a restricted food access regimen (2 h per day) for at least 3 weeks. Food deprived (FD) and control rats were analyzed at different time-points before, during and after the 2 h-food consumption. FD rats showed a marked increase in extracellular DA concentration 80 min before food presentation; this reached the highest level during food consumption, and returned to basal values when food was taken away. This effect was completely abolished by both acute and chronic administration of the CB1R antagonist SR 141716, while the agonist WIN 55,212-2 failed to modify the response of dopaminergic neurons to FD. To evaluate possible changes in CB1R function in FD rats we performed whole cell patch clamp recordings of spontaneous GABAergic IPSCs from pyramidal neurons present in PFC slices. Bath perfusion of WIN 55,212-2 (5 μM) decreased the frequency of sIPSCs in controls, and this effects was reduced in FD rats before food presentation. Moreover, eCB-dependent depolarization-induced suppression of GABAergic sIPSCs (DSI) resulted markedly reduced in FD animals compared to controls. Furthermore, the basal frequency of sIPSC was significantly lower in PFC neurons of FD rats suggesting an altered presynaptic GABA release. Bath application of the D2R agonist quinpirole (1 μM) or the GABA-BR agonist baclofen (10 μM), induced a stronger decrease of sIPSC frequency in FD animals compared to controls suggesting a possible upregulation of these receptors at presynaptic level. Finally, Western blot and immunohistochemical analysis revealed a significant decrease in the expression of CB1Rs in PFC of FD rats compared to controls. Together our data confirm the importance of the eCB system in the control of DA release from VTA to the mPFC, and suggest that the increase in DA output observed in FD rats might be due to a downregulation of CB1R in PFC.
Tipologia:4.2 Abstract in Atti di convegno

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