The mesolimbic dopamine system, which arises in the ventral tegmental area (VTA), is an important neural substrate for opiate reinforcement and addiction. Chronic exposure to opiates is known to produce biochemical adaptations in this brain region. We now show that these adaptations are associated with structural changes in VTA dopamine neurons. Individual VTA neurons in paraformaldehyde-fixed ...

Previously, we demonstrated that the action of the natural alkaloid, ibogaine, to reduce alcohol (ethanol) consumption is mediated by the glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area (VTA). Here we set out to test the actions of GDNF in the VTA on ethanol-drinking behaviors. We found that GDNF infusion very rapidly and dose-dependently reduced rat ethanol, bu...

Glutamatergic innervation of the ventral tegmental area (VTA) and the nucleus accumbens (NA) regulates locomotor activity. The present study was designed to evaluate the involvement of metabotropic glutamate receptors (mGluRs) in motor activity. Agonists selective for each of the three subgroups of mGluRs were microinjected into the VTA or NA, and motor activity was monitored. The group I agoni...

The ventral tegmental area (VTA) plays a critical role in motivation and reinforcement. Kappa and mu opioid receptor (KOP-R and MOP-R) agonists microinjected into the VTA produce powerful and largely opposing motivational actions. Glutamate transmission within the VTA contributes to these motivational effects. Therefore information about opioid control of glutamate release onto VTA neurons is i...

Dopamine (DA) neurons in the midbrain ventral tegmental area (VTA) integrate complex inputs to encode multiple signals that influence motivated behaviors via diverse projections. Here, we combine axon-initiated viral transduction with rabies-mediated trans-synaptic tracing and Cre-based cell-type-specific targeting to systematically map input-output relationships of VTA-DA neurons. We found tha...

Dopaminergic networks modulate neural processing across a spectrum of function from perception to learning to action. Multiple organizational schemes based on anatomy and function have been proposed for dopaminergic nuclei in the midbrain. One schema originating in rodent models delineated ventral tegmental area (VTA), implicated in complex behaviors like addiction, from more lateral substantia...

Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated th...

Dopaminergic neurons in the ventral tegmental area (VTA) are important for the rewarding properties of drugs of abuse, including ethanol. We previously demonstrated that ethanol excites VTA neurons and that ethanol reduces the amplitude of the after hyperpolarization (AHP) that follows spontaneous action potentials. Because the small conductance calcium-activated potassium current (SK) is a com...

Ventral tegmental area (VTA) GABA neurons are critical substrates modulating the mesocorticolimbic dopamine system implicated in natural and drug reward. The aim of this study was to evaluate the effects of ethanol on glutamatergic and GABAergic modulation of VTA GABA neuron electrical synaptic transmission. We evaluated the effects of systemic ethanol (0.05-2.0 g/kg i.p.), the N-methyl-D-aspar...

The ventral tegmental area dopamine (DA VTA) neurons have the spontaneous tonic activity and an alteration of firing pattern from tonic to burst accelerates dopamine transmission more effectively in the mesoaccumbal dopaminergic system, leading to the reinforcing process of drugs of abuse such as alcohol and nicotine. In the present study, we examined whether a persistent Na+ current would cont...