Proportion of cocaine-coding neurons in the orbitofrontal cortex determines individual drug preferences

SUMMARY Cocaine addiction is a harmful preference for drug use over and at the expense of other nondrug-related activities. Here we identify in the orbitofrontal cortex (OFC) – a prefrontal region involved in choice and decision-making – a mechanism that explains individual preferences in rats between cocaine use and an alternative, nondrug action. We found that initiation of these actions is selectively encoded by two non-overlapping populations of OFC neurons, and that the relative size and differential pre-choice activity of the cocaine action-coding population determine an individual preference, a larger size and a higher pre-choice activity being associated with cocaine preference. A larger size is a structural feature that may confer to a population of OFC neurons a competitive advantage during choice in favor of the encoded action. Such structural encoding also explains two other major defining features of an individual drug preference, its stability over time and its resistance to change.