Addictive drugs primarily alter the function of receptor-gated ion channels (nicotine, alcohol), neurotransmitter transporters (cocaine, amphetamine) or G protein–coupled receptors (opiates, cannabinoids), and these initial events lead to activation of signaling pathways that result in the activation of the downstream protein kinases described in this review. With the exception of alcohol, drugs of abuse do not appear to directly modulate the function of these kinases. In the case of alcohol, there are some data indicating alcohol inhibition of PKC but only in a highly reduced in vitro system using artificial lipid membranes and purified proteins.278 Convincing evidence for in vivo activation by intoxicating doses of ethanol is lacking however.
