Figure 5
From: Diversity of Dopaminergic Neural Circuits in Response to Drug Exposure
Drugs of abuse act in different ways to increase DA concentrations in downstream targets of the VTA. Pictured here is a VTA DA neuron projecting to the NAc. Ethanol acts directly on VTA DA neurons to increase VTA cell firing, increase Ih, and increase GIRK activity. This increase in activity leads to increased DA release. Ethanol also has effects on VTA GABA interneurons. Nicotine acts on VTA DA neurons themselves through the ligand-gated ion channel, nAChRs. Nicotine also has effects on GABA interneurons and glutamatergic afferents. Morphine acts indirectly through GABA interneurons to increase VTA DA activity. Morphine binds to MORs to decrease IPSC frequency and decrease GABAergic cell firing. This decrease in GABAergic tone disinhibits VTA DA neurons, increasing DA concentrations in the NAc. Cocaine increases concentrations of DA in the NAc by inhibiting DAT function at the VTA DA terminal. Interestingly, acute administration of ethanol, morphine, and cocaine was shown to enhance glutamatergic synaptic strength, as seen through an increase AMPA/NMDA ratio. DA, dopamine; DAT, dopamine transporter; GIRK, G protein-coupled inwardly rectifying potassium channels; Ih, hyperpolarization-activated cation channel current; IPSC, inhibitory post-synaptic current; MOR, μ-opioid receptor; NAc, nucleus accumbens; VTA, ventral tegmental area.
