Investigation of noradrenergic inputs to midbrain monoaminergic nuclei

National Institute On Drug Abuse

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Abstract

The release of noradrenaline in midbrain monoaminergic nuclei, including the dorsal raphe nucleus (DR), ventral tegmental area (VTA), and substantia nigra pars compacta (SNc) excites serotonin and dopamine neurons through the activation of excitatory 1-adrenergic receptors, enhancing action potential firing and neurotransmitter release. The release of noradrenaline from axon terminals is inhibited through the activation of 2-adrenergic autoreceptors. Despite this influential role, the most basic questions regarding noradrenaline-dependent excitation remain unanswered, stemming from an incomplete characterization of 1- and 2-adrenergic receptor signaling at a synaptic level and within the context of the brain circuits and behavior. This study identifies and characterizes ion channels that regulate 5-HT neuron action potential firing. On-going work investigates the role of noradrenergic inputs to the DR in reward-, learning, and affect-related behaviors.