Smith J B
School of Pharmacy, Mercer University - Atlanta, 3001 Mercer University Drive, Atlanta, GA 30341, USA.
Eur J Pharmacol. 1999 Dec 3;385(2-3):89-97. doi: 10.1016/s0014-2999(99)00717-7.
Behavioral effects of diazepam were studied in rats responding in different daily sessions using different operant chambers and manipulanda. In one experiment, key pressing was maintained in a first session under a 40-response fixed-ratio schedule; lever pressing was maintained in a second session under a 40-response fixed-ratio schedule; and a third session consisted of a multiple schedule comprising both key and lever pressing maintained under a 40-response fixed-ratio schedule. In a second experiment, the first session consisted of a multiple schedule with both key and lever pressing maintained under a 40-response fixed-ratio schedule and the second session consisted of lever pressing maintained under a 40-response fixed-ratio schedule. After studying effects of widely spaced injections of diazepam (0.3-3.0 mg/kg) on responding for each separate schedule, animals received 1.7 mg/kg/day diazepam in order to study chronic effects of the diazepam on behavior among the different schedule-conditions. In both experiments, tolerance to rate-decreasing effects of diazepam in a particular schedule component did not extend to any other schedule component when the manipulandum or chamber was different, but did extend to other schedule components when the manipulandum or chamber was the same. These results suggest that behavioral effects of chronically administered diazepam were influenced not only by pharmacologic processes, but also by learned relationships among its interoceptive effects, reinforcement contingencies, and particular behavioral environments.