The lateral hypothalamus (LH) has long been known to implicate in the addictive behaviors of drugs of abuse. The ventral tegmental area (VTA) is a major area of the mesolimbic system that is strongly involved in the development of morphine sensitization. The current study aimed to examine the role of intra-VTA orexin receptors in the LH stimulation-induced sensitization to the antinociceptive r...

Salient but aversive stimuli inhibit the majority of dopamine (DA) neurons in the ventral tegmental area (VTA) and cause conditioned place aversion (CPA). The cellular mechanism underlying DA neuron inhibition has not been investigated and the causal link to behavior remains elusive. Here, we show that GABA neurons of the VTA inhibit DA neurons through neurotransmission at GABA(A) receptors. We...

Phasic increases and decreases in dopamine (DA) transmission encode reward prediction errors thought to facilitate reward-related learning, yet how these signals guide action selection in more complex situations requiring evaluation of different reward remains unclear. We manipulated phasic DA signals while rats performed a risk/reward decision-making task, using temporally discrete stimulation...

Appetitive behaviors of rats were monitored in a runway situation following central infusions of neuroactive substances into brain areas implicated in electrical self-stimulation. Microinjections of the dopamine antagonist cis-flupentixol or the cholinergic antagonist atropine into the nucleus accumbens (Acb) severely reduced the approach speed and anticipatory shuttlebox activity while leaving...

Leptin acts on the ventral tegmental area (VTA) to modulate neuronal function and feeding behavior in rats and mice. To identify the intracellular effectors of the leptin receptor (Lepr), downstream signal transduction events were assessed for regulation by direct leptin infusion. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) and phosphorylated extracellular signal-...

Axonal collateralization of substantia nigra (SN) and ventral tegmental area (VTA) neurons was studied in the rat with the multiple retrograde labeling technique using fluorescent dyes. Injections of nuclear yellow, granular blue, and propidium iodide were made into the caudate-putamen, septum, and frontal cortex and cells were found to be single, double, and triple labeled in the SN-VTA. Cells...

Dopamine neurons in the ventral tegmental area (VTA) represent a critical site of synaptic plasticity induced by addictive drugs. Orexin/hypocretin-containing neurons in the lateral hypothalamus project to the VTA, and behavioral studies have suggested that orexin neurons play an important role in motivation, feeding, and adaptive behaviors. However, the role of orexin signaling in neural plast...

Active response to either natural or pharmacological reward causes synaptic modifications to excitatory synapses on dopamine (DA) neurons of the ventral tegmental area (VTA). Here, we examine these modifications using nicotine, the main addictive component of tobacco, which is a potent regulator of VTA DA neurons. Using an in vivo electrophysiological technique, we investigated the role of key ...

The ventral tegmental area (VTA) has been implicated in a number of psychiatric disorders, including schizophrenia, depression, and bipolar disorder. One major regulator of the mesolimbic dopaminergic system is the medial prefrontal cortex (mPFC), which makes direct and indirect connections to the hippocampus and amygdala, as well as directly to the VTA. The mPFC is comprised of two subregions:...

Contemporary preclinical models suggest that abnormal functioning of a brain network consisting the hippocampus, midbrain and striatum plays critical role in pathophysiology schizophrenia. Previous neuroimaging studies examined individual aspects this model schizophrenia patients individuals at clinical high risk for psychosis. However, exact has not been translated to human with therefore it i...