Extra (non-contingent) food does not affect behavioral tolerance to XXXX 's rate-decreasing effects.

@entity35 @entity2254
UNASSIGNED: Tolerance refers to the diminished effect of a drug following its repeated administration such that a larger dose is needed to obtain the initial effect. Tolerance to a drug's effects on operant behavior is more likely to develop when initial drug administration results in a loss of reinforcement. It remains unknown how offsetting loss of reinforcement influences the development of tolerance. Providing extra (non-contingent) food pellets was hypothesized to impede the development of tolerance to effects of a repeatedly administered dose of @entity2254 that reduced the number of food pellets earned by @entity35 . A multiple schedule with two variable-interval (VI) 60-s components resulting in food delivery was used to maintain lever pressing. Extra food pellets were provided in one of those components according to a variable-time (VT) 120-s or a VT 30-s schedule for separate groups of @entity35 (n=6 for each group). Effects of @entity2254 (0.1-3.0mg/kg) were tested before (acute) and during (chronic) injections (45days) of an individually selected, repeatedly administered dose that reduced the number of food pellets earned by at least 50% compared to when saline was tested acutely. There was a dose-dependent decrease in lever-press rates and food pellets earned. The development of tolerance was quantified by dividing the area-under-the-curve (AUC) of the chronic dose-effect function by the AUC of the acute dose-effect function. Tolerance developed to a similar extent in components with and without extra food pellets for @entity35 in both groups. These results indicate that offsetting reinforcement loss, at least as studied here, did not differentially affect tolerance development.
