‘Ups, downs, and sideways’ of dopamine in drug addiction

Under the title “Dopamine ‘ups and downs’ in addiction revisited”, Samaha et al. discuss the alteration of dopamine signaling evoked by repeated cocaine exposure, which may underlie addictive behavior [ 1. Samaha A.-N. et al. Dopamine ‘ups and downs’ in addiction revisited. Trends Neurosci. 2021; 44: 516-526 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ]. Focusing on the commonality of addictive drugs, the pharmacologically evoked dopamine transients in the nucleus accumbens (NAc), two contrasting views on adaptive changes in dopamine transmission become apparent. On the one hand, prolonged exposure to cocaine can blunt dopamine elevations (a.k.a. tolerance), which the individual would try to overcome by taking more drugs. On the other hand, when a subject is exposed intermittently, dopamine levels in response to the drug and drug cues may become larger, thereby strongly driving the ‘wanting’ of drugs. In discussing the various behavioral paradigms, such as a clever intermittent cocaine self-administration model, the authors conclude in favor of the ‘up’ hypothesis of incentive saliency that also better fits human intake patterns.