Abstract
Adiponectin, a metabolic hormone secreted by adipocytes, can cross the blood–brain barrier to act on neurons in different brain regions, including those involved in stress-related disorders. Here we show that dopamine neurons in the ventral tegmental area (VTA) express adiponectin receptor 1 (AdipoR1). Intra-VTA infusion of adiponectin or the adiponectin mimetic AdipoRon in wild-type mice decreases basal dopamine neuron population activity and firing rate and reverses the restraint stress-induced increase in dopamine neuron activity and anxiety behavior. Adiponectin haploinsufficiency leads to increased dopamine neuron firing and anxiety behavior under basal conditions. Ablation of AdipoR1 specifically from dopamine neurons enhances neuronal and anxiogenic responses to restraint stress. The effects of intra-VTA infusion of adiponectin on neuronal activity and behavior were abolished in mice lacking AdipoR1 in dopamine neurons. These observations indicate that adiponectin can directly modulate VTA dopamine neuron activity and anxiety behavior, and that AdipoR1 is required for adiponectin-induced inhibition of dopamine neurons and anxiolytic effects. These results strengthen the idea of adiponectin as a key biological factor that links metabolic syndrome and emotional disorders.
Highlights
The mesolimbic dopamine system, originating from dopamine neurons in the ventral tegmental area (VTA), is a key neural substrate for reward processing and emotional responses [1]
To determine whether adiponectin receptor 1 (AdipoR1) and AdipoR2 are expressed in VTA dopamine neurons, we first performed in situ hybridization with radioactive cRNA probes to examine the expression patterns of AdipoR1 and AdipoR2 mRNA in the VTA
We found that AdipoR1 mRNA was abundant in the VTA, whereas AdipoR2 mRNA was almost undetectable in this region (Fig. 1a)
Summary
The mesolimbic dopamine system, originating from dopamine neurons in the ventral tegmental area (VTA), is a key neural substrate for reward processing and emotional responses [1]. It has been shown that midbrain dopamine neurons respond directly to a distinct set of metabolic hormones and relay signals from periphery to mesolimbic neural circuits [9,10,11, 14]. These studies have mainly focused on the functions of metabolic hormones in food rewards and energy metabolism. The adipocyte-derived hormone leptin was found to regulate VTA dopamine neuron firing and anxiety-related
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