Impaired Striatal GABA Outflow in Leptin Receptor Deficient Rats - The Role of Glucose and KATP Channels

Sonya Neto, Philipp Capetian, Anett Schumacher, Andreas Georg Christian Moser


The leptin receptor (LepR) is considered to be crucial for feedback mechanisms of food intake, body weight and glucose homeostasis. Its activity has been linked to ATP-dependent potassium (KATP) channels that couple bioenergetic metabolism to membrane excitability. In previous studies, it has been demonstrated that glucose modulates striatal γ-aminobutyric acid (GABA) outflow through KATP channels in slice preparations of the rat caudate nucleus. Our goal was to assess the impact of the LepR mutation on this mechanism. Slices of the caudate nucleus from heterozygous (Fa/fa) and homozygous (fa/fa) Zucker diabetic fatty rats (ZDF) and control Wistar rats were incubated with two different doses of glucose. GABA outflow was measured by means of high performance liquid chromatography (HPLC) with electrochemical detection. Glucose reduction (from 10 to 7 mM) resulted in a decreased GABA outflow in Wistar rats. In contrast, GABA outflow of striatal slices of LepR Fa/fa and LepR fa/fa rats remained nearly unchanged when extracellular glucose levels were lowered. The KATP channel blocker glibenclamide (Glb, 10 µM) prevented GABA outflow reduction in control rats at glucose concentrations of 7 mM, implying the involvement of KATP-channels. However, no change of GABA outflow was observed in LepR mutant rats after Glb addition. Although heterozygous ZDF rats possess one healthy LepR allele, no difference could be observed between lean heterozygous and obese homozygous animals. In summary, we demonstrate for the first time an impaired striatal GABA outflow in response to changing glucose levels in heterozygous and homozygous LepR mutant rats.

Original languageEnglish
JournalOpen Journal of Neuroscience
Issue number2017
Publication statusPublished - 2017

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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