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Drug Activation of Dopaminergic Neurons SIGMA-ALDRICH Drug Activation of Dopaminergic Neurons The main mechanism responsible for the reinforcing properties of most abused drugs is the direct or indirect activation of dopaminergic neurons in the ventral tegmental area (VTA). This figure represents a dopaminergic neuron in the VTA as well as a GABAergic interneuron and a GABAergic projection neuron with a recurrent collateral. Whereas, nicotine increases the firing rate of dopaminergic neurons in the VTA by activating nicotinic acetylcholine receptors located on these cells, other drugs of abuse activate dopaminergic neurotransmission by inhibiting GABAergic transmission in the VTA. Stimulation of m opioid receptors, GABAA receptors, or CB1 cannabinoid receptors on VTA GABAergic neurons reduces GABA transmission, which increases the firing rate of dopaminergic neurons via disinhibition.
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