Blockade of astrocytic glutamate uptake in the prefrontal cortex induces anhedonia.

摘要: Major depression is associated with both dysregulated glutamatergic neurotransmission and fewer astrocytes in limbic areas including the prefrontal cortex (PFC). These deficits may be functionally related. Notably, regulate glutamate levels by removing from synapse via transporter (GLT-1). Previously, we demonstrated that central blockade of GLT-1 induces anhedonia c-Fos expression PFC. Given role PFC regulating mood, hypothesized alone would sufficient to induce rats. We microinjected inhibitor, dihydrokainic acid (DHK), into examined effects on mood using intracranial self-stimulation (ICSS). At lower doses, intra-PFC DHK produced modest increases ICSS thresholds, reflecting a depressive-like effect. higher resulted cessation responding. conducted further tests clarify whether this total responding was related an anhedonic state (tested sucrose intake), nonspecific result motor impairment (measured tape test), or seizure activity electroencephalogram (EEG)). The highest dose increased latency begin drinking without altering intake. Furthermore, neither nor evidence observed test EEG recordings. A decrease reward value followed complete suggests anhedonic-like effect DHK; conclusion substantiated drinking. Overall, these results suggest astrocytic uptake produce anhedonia, core symptom depression.