Jl. Wiley et al., DIFFERENTIAL-EFFECTS OF CLOZAPINE AND PIMOZIDE ON FIXED-RATIO RESPONDING DURING REPEATED DOSING, Pharmacology, biochemistry and behavior, 48(1), 1994, pp. 253-257
Previous research has shown that the differential development of toler
ance to the disruption of operant responding produced by repeated dosi
ng with pimozide (PMZ) or clozapine (CLZ) can distinguish these two dr
ugs. In the present study, the effects of PMZ (1 mg/kg) and CLZ (10 mg
/kg) on response rate and response duration in rats lever pressing for
food reward under a fixed-ratio 30 (FR-30) operant schedule were exam
ined. PMZ suppressed response rates across all 10 days of drug dosing;
CLZ produced an initial response rate decrease, with partial recovery
(50%) occurring within the 10 day period. Similarly, PMZ produced an
increase in response duration that persisted into the postdrug vehicle
-injection period, while CLZ did not significantly change response dur
ation. The prolonged suppression of FR responding produced by PMZ is s
imilar to the lack of tolerance to this drug in other types of operant
schedules. In contrast, CLZ's effects on response rate are schedule d
ependent. These results suggest that changes in response duration with
repeated dosing may more reliably differentiate typical and atypical
neuroleptics than do changes in response rate under FR schedules.