Fig. 1.

Classical intravenous self-administration dose–response and dose–intake functions (A) and theoretical expression of individual differences as horizontal (B) or vertical (C) shifts of these functions. The two models predict two different drug-vulnerable (filled circles) and drug-resistant (open circles) phenotypes. In the case of a horizontal shift, a vulnerable subject (the one leftward shifted) will have a higher number of responses (B, top) in the active device (the ones delivering the drug) only for low unitary drug doses. In the case of a vertical shift (C, top), a vulnerable subject (the one upward shifted) will have higher responses in the active device across doses. As a consequence, the leftward shifted individuals will have the lowest drug intake (B, middle), whereas the upward shifted subjects will have the highest one (C,middle). Furthermore, taking into account all of the subjects, the correlation between the number of responses in the active device at doses in the ascending (for example, the 2dose) and descending (for example, the 8dose) limbs of the dose–response function will be negative if a horizontal shift (B,bottom) occurs and positive in the case of a vertical one (C, bottom).