A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats

Abstract

This study examined whether continued access to methamphetamine or food reinforcement changed economic demand for both. The relationship between demand elasticity and cue-induced reinstatement was also determined. Male Long-Evans rats were lever pressed under increasing fixed-ratio requirements for either food pellets or methamphetamine (20 μg/50 μl infusion). For two groups, demand curves were obtained before and after continued access (12 days, 2-h sessions) to the reinforcer under a fixed-ratio 3 schedule. A third group was given continued access to methamphetamine between determinations of food demand and a fourth group abstained from methamphetamine between determinations. All groups underwent extinction sessions, followed by a cue-induced reinstatement test. Although food demand was less elastic than methamphetamine demand, continued access to methamphetamine shifted the methamphetamine demand curve upward and the food demand curve downward. In some rats, methamphetamine demand also became less elastic. Continued access to food had no effect on food demand. Reinstatement was higher after continued access to methamphetamine relative to food. For methamphetamine, elasticity and reinstatement measures were correlated. Continued access to methamphetamine, but not food, alters demand in ways suggestive of methamphetamine accruing reinforcing strength. Demand elasticity thus provides a useful measure of abuse liability that may predict future relapse to renewed drug-seeking and drug use.

Fig. 1

Upper panel: Mean number of food (closed circles) and methamphetamine (open circles) reinforcer deliveries plotted as a function of the prevailing response requirement on a log-log scale. Curved lines represent the best-fit functions using the exponential demand equation. Lower panel: Normalized demand curves for food and methamphetamine.

Fig. 2

Mean (± SEM) consumption of food or methamphetamine during the 12 sessions of continued access. Symbols represent significant differences (p < .05) during Sessions 7–12 relative to Session 1 (*) and also Sessions 8, 11, and 12 relative to Sessions 2 and 3 (#).

Fig. 3

Mean (± SEM) number of food or methamphetamine reinforcers earned as a function of the prevailing response requirement for each group in the first (closed bars) and second (open bars) determinations of demand. The (#) symbol represents a significant (p < .001) main effect of determination. The (*) symbol represents significant differences (p < .05) between determinations at individual ratios.

Fig. 4

Normalized food and methamphetamine demand curves as a function of group and determination.

Fig. 5

Individual subject data from the three rats in the MMM group that demonstrated the greatest increase in methamphetamine intake during continued access. The upper left panel shows consumption during continued-access sessions. The remaining panels show demand curves for methamphetamine before (first; closed symbols – solid lines) and after (second; open symbols – dashed lines) continued access to methamphetamine.

Fig. 6

Upper panel: Mean (± SEM) of the logarithms of the number of responses made during the first 10 sessions of extinction, sorted into 2-session blocks. Lower panel: The data in the upper panel are expressed as a proportion of Block 1 responding.

Fig. 7

Mean (± SEM) number of responses made during the final two sessions of extinction (averaged in one column) and the cue-induced reinstatement test as a function of group. The relative increase in responding from extinction to reinstatement was significantly less (p < .05) for the FFF group (*) relative to the MMM group.