Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis

Rationale: It has been proposed that the ascending 5-hydroxytryptaminergic (5-HTergic) pathways are involved in "impulse control". Previous experiment s have shown that rats whose 5-HTergic pathways have been destroyed are mor e liable than intact rats to select a smaller, immediate reinforcer rather than a larger, delayed reinforcer (impulsive choice). However, it remains u nclear whether this effect of central 5-HT depletion reflects a change in t he rate of time discounting (i.e. a change in the rate at which reinforcers become devalued as a function of delay) or a change in sensitivity to rein forcer size. Objective: We examined the effect of central 5-HT depletion on time discounting using a quantitative model of inter-temporal choice (muit iplicative hyperbolic model), which enables effects on time discounting to be differentiated from effects on sensitivity to reinforcer size. Methods: Rats received injections of 5,7-dihydroxytryptamine into the dorsal and med ian raphe nuclei or sham lesions. They were trained to press two levers for food-pellet reinforcers in a discrete-trials adjusting-delay schedule. In free-choice trials, selection of lever A resulted in a brief fixed delay (d (A)) followed by delivery of one pellet; selection of lever B resulted in a longer variable delay (d(A)) followed by delivery of two pellets; d(B) was adjusted in accordance with the subject's choices. The value of d(A) was v aried (0.5-8.0 s) in successive phases of the experiment, and the indiffere nce value of d(B) was determined in each case. Results: In both groups, the indifference value of d(B) was linearly related to the value of d(A), in a ccordance with the multiplicative hyperbolic model. The lesioned group show ed shorter indifference delays than the sham-lesioned group, this being ref lected in a parallel displacement of the linear indifference function. In b oth experiments, the levels of 5 HT and 5-hydroxyindole-acetic acid were re duced in the brains of the lesioned rats, but the levels of noradrenaline a nd dopamine were not altered. Conclusions: According to the multiplicative hyperbolic model, parallel displacement of the linear indifference function uniquely specifies a change in time discounting. Thus these results indica te that central 5-HT depletion results in an increase in the rate of time d iscounting for food reinforcers.