Addictive substances can be generally grouped into drugs that interact with monoamine transporters, activate Gi/o-coupled protein receptors, or alter the function of ion channels and ionotropic receptors.7 The psychostimulants cocaine and amphetamines both increase extracellular levels of monoamines, such as dopamine, but they act through different molecular mechanisms: cocaine inhibits the cell surface dopamine transporter (DAT), while amphetamines inhibit DAT and also stimulate dopamine release from vesicles allowing reverse transport of dopamine through DAT. Nicotine also has stimulatory effects through activation of nicotinic acetylcholinergic (nACh) receptors, which are ligand-gated cation channels. Opiates and cannabinoids activate different Gi/o-coupled protein receptors and appear to activate some similar downstream signaling events. Ethanol alters the function of several ion channels and ionotropic receptors and often produces different effects compared with other addictive drugs. We will examine the effects of cocaine, amphetamines, nicotine, opiates, cannabinoids, and ethanol on protein kinases, summarizing the available studies. Importantly, we will also review the effects of manipulating protein kinases in animal models with an emphasis on identifying signaling pathways that could provide new targets for treatment of addiction.
