Figure 1.

A summary of the effects of different cocaine self-administration experiences on cocaine intake, and on the development of addiction-like behaviors (see Table 1). Representative patterns of cocaine intake and estimated brain concentrations of cocaine produced by different self-administration procedures are on the top left. In the first 1–2 hours, LgA animals achieve higher brain cocaine concentrations than ShA only after escalation of intake. Under LgA and ShA conditions, there are some fluctuations in brain cocaine concentrations, reflecting the inter-injection interval, which is influenced by unit dose. This is consistent with findings that there are cyclical fluctuations in dopamine-related electrochemical signals in the nucleus accumbens when rats are self-administering cocaine under continuous-access conditions (Gratton and Wise 1994; also see Keramati et al. 2017). However, the fluctuations in brain cocaine concentrations under LgA and ShA are very small relative to the large spikes obtained with IntA. Note also that LgA and ShA conditions would produce high brain concentrations of drug throughout each self-administration session, but concentrations would then drop until the next session. This would model the intermittency of drug use between bouts of consumption reported in human cocaine users (see text). However, human cocaine use is intermittent both between and within bouts, and this is modeled by intermittent access self-administration. The top right panel shows the relative total cocaine intake/session produced by these different procedures (and the inset shows the pattern of change in consumption over time). Below that, addiction-like behaviors typically assessed in laboratory animals are listed and the relative ability of the different self-administration procedures to produce each behavior is indicated. When arrows are used, a single arrow indicates the ‘baseline’ effect, and then the number of arrows indicates the relative size of a given effect. When quantitative comparisons were not possible a “Yes” or “No” indicates whether a procedure produces a given effect. Horizontal lines with a double arrowhead indicate no effect, and the downward and upward facing arrowheads a decrease and increase, respectively. Dashes indicate no data are available.

The figure highlights two main points discussed in the text. (1) LgA results in greater drug consumption than all the other procedures. (2) IntA experience is more effective in increasing motivation for drug, based on a number of metrics, than ShA or LgA experience, despite much less consumption than LgA.