Table 1.

Main classes of drugs of abuse, their main molecular targets, and some of the mechanism(s) by which they increase DA in NAc (44)

DrugTargetMechanism for DA increases
Stimulant drugs (cocaine, amphetamine, methamphetamine)DATBlocks DAT on the terminals of DA projecting neurons from VTA to NAc (cocaine) or releases DA from the vesicles of DA terminals (methamphetamine, amphetamine)
Opioids (heroin, opioid analgesics)MORDisinhibits VTA DA neurons by inhibiting GABA interneurons that contain MOR in the VTA or directly activates NAc neurons that contain MOR
Nicotine (cigarettes and other tobacco products)Nicotinic receptors (predominantly α4β2 subtype)Directly activates VTA DA neurons by stimulating their nicotine receptors and indirectly activates them by stimulating the nicotine receptors in glutamatergic terminals to VTA DA neurons
Alcohol and inhalantsMultiple targets, including GABA and glutamate receptorsFacilitates GABAergic neurotransmission, which may disinhibit VTA DA neurons from GABA interneurons or may inhibit glutamate terminals that regulate DA release in Nac
Cannabinoids (marihuana)Cannabinoid CB1 receptorsRegulates dopaminergic signaling through CB1R in NAc neurons and in GABA and glutamate terminals to NAc
  • DAT, DA transporter; MOR, μ-opioid receptor.