Influence of Neuropeptide Y and antidepressants upon cerebral monoamines involved in depression: An in vivo electrochemical study

Neuropeptide Y (NPY) and its receptors are present in the peripheral as well as the central nervous system (CNS). In vitro data have indicated NPY as an important mediator in the regulation of different diseases e.g. related to obesity, anxiety, depression, pain, memory loss and sleep disorders. In particular, studies of NPY levels in the cerebral spinal fluid (CSF) of depressed patients have shown a significant reduction of NPY levels when compared to control subjects. In addition, decreased concentrations of NPY were measured in the brain of suicide victims. These studies suggest that a reduction in cerebral NPY function may be associated with depressive symptoms. In the present work, a putative interaction between NPY, the catecholaminergic and serotonergic systems has been analysed by means of in vivo Differential Pulse Voltammetry (DPV) with treated carbon fibre micro electrodes (mCFE). It appeared that DPV with mCFE is an efficacious tool to monitor in vivo basal levels of catechols (Peak 2) and indoles (Peak 3) in discrete brain regions of rodents. Furthermore, it is shown that the peptidergic signal (Peak 5) simultaneously recorded with Peaks 2 and 3 in the amygdala could correspond to the oxidation of basal endogenous NPY. In addition, pharmacological treatments performed in vivo with exogenous NPY and with Y1 receptor antagonist BIBP3226 have indicated that these compounds interact positively with endogenous catecholaminergic and serotoninergic systems, in a way similar to that of the antidepressants imipramine and fluoxetine. In addition, the observed decrease of endogenous Peak 5 after treatment with imipramine or fluoxetine could be related to the concomitant stimulation of the catecholaminergic system with consequent reduced need for endogenous NPY. This would imply that NPY could be one of the endogenous chemicals acting on the maintenance of the mood. Thus, an antidepressant therapeutic potential of NPY and related compounds (e.g. BIBP3226) could be proposed.

► Differential Pulse Voltammetry [DPV] with treated carbon fibre micro electrodes (mCFE) is an efficacious tool to monitor in vivo basal levels of catechols (Peak 2) and indoles (Peak 3) in discrete brain regions of rodents.
► Furthermore, it is shown that the peptidergic signal (Peak 5) that simultaneously recorded with Peaks 2 and 3 in the amygdala could correspond to the oxidation of basal endogenous Neuropeptide Y [NPY].
► Pharmacological treatments performed in vivo with exogenous NPY and with Y1 receptor antagonist Thomae have indicated that these compounds interact positively with endogenous catecholaminergic and serotoninergic systems, in a way similar to that of the antidepressants imipramine and fluoxetine.
► In addition, the observed decrease of endogenous Peak 5 after treatment with imipramine or fluoxetine could be related to the concomitant stimulation of the catecholaminergic system with consequent reduced need for endogenous NPY.
► This would imply that NPY could be one of the endogenous chemicals acting on the maintenance of the mood. Thus, an antidepressant therapeutic potential of NPY and related compounds (e.g. Thomae) could be proposed.