Alterations in blood glucose and plasma glucagon concentrations during deep brain stimulation in the shell region of the nucleus accumbens in rats

Charlene Diepenbroek,Susanne E La Fleur,Geoffrey Van Der Plasse,Mireille J Serlie,Andries Kalsbeek,Leslie Eggels,Eric Fliers,Merel Rijnsburger,Damiaan Denys,Matthijs G P Feenstra

doi:10.3389/fnins.2013.00226

Abstract

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is an effective therapy for obsessive compulsive disorder (OCD) and is currently under investigation as a treatment for eating disorders. DBS of this area is associated with altered food intake and pharmacological treatment of OCD is associated with the risk of developing type 2 diabetes. Therefore we examined if DBS of the NAc-shell (sNAc) influences glucose metabolism. Male Wistar rats were subjected to DBS, or sham stimulation, for a period of 1 h. To assess the effects of stimulation on blood glucose and glucoregulatory hormones, blood samples were drawn before, during and after stimulation. Subsequently, all animals were used for quantitative assessment of Fos immunoreactivity in the lateral hypothalamic area (LHA) using computerized image analysis. DBS of the sNAc rapidly increased plasma concentrations of glucagon and glucose while sham stimulation and DBS outside the sNAc were ineffective. In addition, the increase in glucose was dependent on DBS intensity. In contrast, the DBS-induced increase in plasma corticosterone concentrations was independent of intensity and region, indicating that the observed DBS-induced metabolic changes were not due to corticosterone release. Stimulation of the sNAc with 200 μA increased Fos immunoreactivity in the LHA compared to sham or 100 μA stimulated animals. These data show that DBS of the sNAc alters glucose metabolism in a region- and intensity- dependent manner in association with neuronal activation in the LHA. Moreover, these data illustrate the need to monitor changes in glucose metabolism during DBS-treatment of OCD patients.

Highlights

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is used to treat obsessive compulsive disorder (OCD), depression and addiction (Denys et al, 2010; Bewernick et al, 2012; Muller et al, 2013) and is currently under investigation for the treatment of eating-disorders
We hypothesized that the neural connection between the shell region of the NAc (sNAc) and pancreas is functional in glucose metabolism
This study shows for the first time the effects of electrical stimulation in the sNAc on neural activity in the lateral hypothalamic area (LHA) and on glucose metabolism

Summary

INTRODUCTION

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is used to treat obsessive compulsive disorder (OCD), depression and addiction (Denys et al, 2010; Bewernick et al, 2012; Muller et al, 2013) and is currently under investigation for the treatment of eating-disorders (eg., Halpern et al, 2008). Effective pharmacological treatment of OCD, such as anti-depressants and serotonin reuptake inhibitors target the dopaminergic- and serotoninergic system This suggests that modulation of these neurotransmitter systems could well be involved in the effects of DBS. DBS of the NAc has been associated with changes in food intake (van der Plasse et al, 2012; Halpern et al, 2013) In light of these findings, and the current interest in DBS as a treatment for eating-disorders (Benabid and Torres, 2012), it is imperative to determine whether DBS might influence glucose metabolism and induce side effects. We hypothesized that the neural connection between the sNAc and pancreas (and liver) is functional in glucose metabolism To investigate this hypothesis, we implanted stimulation electrodes in the sNAc of rats and studied the effects of local stimulation on blood glucose and glucoregulatory hormones. This study shows for the first time the effects of electrical stimulation in the sNAc on neural activity in the LHA and on glucose metabolism

METHODS

ANALYTICAL METHODS

RESULTS