Clozapine-induced acetylcholine release in the rat prefrontal cortex, nucleus accumbens and striatum does not develop tolerance

1. 1.- The present study investigated the effects of a long-term treatment with clozapine on the clozapine-induced ACh overflow in the rat brain. 2. 2.- Ten male Wistar rats received a daily ip clozapine injection (20 mg/Kg) for 21 days. Triple brain microdialysis was used to monitor the effects of the first and last injections (reinsertion group; n = 5) or just the last injection (single insertion group; n = 5) on the ACh outflow in the PFC, NAC, and STR. 3. 3.- In the reinsertion group the ACh release changed neither in the PFC [310 ±77% after the first Vs 329 ± 54% after the last injection; (Fl/40: 0.3; NS) ] nor in the STR [144 ± 27% Vs 163 ± 12%; (F1/40: 1.1; NS) ] but was larger in the NAC after the chronic treatment [142 ± 20% Vs 211 ± 28%; [F1/40: 15.9; p