Different involvement of ventral and dorsal norepinephrine pathways on norepinephrine reuptake inhibitor-induced locomotion and antidepressant-like effects in rats

Two experiments were performed to investigate the involvements of ventral and dorsal norepinephrine bundle (VNB and DNB) in a selective norepinephrine reuptake inhibitor (NRI) reboxetine (RBX)-induced locomotion and antidepressant-like effects. Rats in the Experiment 1 received a local brain injection of 6-hydroxydopamine (6-OHDA) or an intraperitoneal injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to lesion their VNB or DNB, respectively. Acute effects of RBX (10 mg/kg, i.p.) on the locomotor activity and the forced swim test (FST) were measured 14 days after the lesion. In Experiment 2, activities of the norepinephrine transporter (NET) and the protein kinase C (PKC) in cortex, hippocampus, and locus coeruleus (LC) were detected by western blot after 14 days chronic RBX treatment. Results showed that the antidepressant-like effect of RBX was blocked in VNB lesion but augmented in DNB lesion, and was not relevant to the RBX-induced hypoactivity. Fourteen-days RBX treatment altered the activities of NET and PKC in LC but not hippocampus or cortex. The possible involvement of VNB and DNB in the RBX-induced antidepressant-like effect is discussed.

► The antidepressant effect of RBX was blocked by the VNB lesion but augmented by the DNB lesion.
► The antidepressant-like activity of RBX found was unlikely caused by any of the locomotion effects.
► After 14 days RBX treatment, the activities of NET and PKC were affected in the LC only.