Figure 3.

D2 receptors (D2R) remain inhibitory following repeated METH. (A) In slices prepared from mice treated with repeated saline, a METH challenge in vivo produced inhibition of FM1-43 destaining that was reversed by the D2R antagonist sulpiride (SULP) in vitro. (B) Distribution of mean t_1/2 of release for FM1-43 destaining curves shown in panel A. n=188–325 puncta; ***p<0.001 compared to control (Veh), Mann-Whitney. (C) Individual terminal responses in saline-treated controls following a challenge with METH in vivo with and without SULP. Repeated methamphetamine produced more inhibition at the slowest-releasing terminals (greater t_1/2). (D) On withdrawal day 10 following repeated METH, a METH challenge in vivo accelerated corticostriatal release. The addition of SULP in vitro further accelerated release to control halftimes. (E) Distribution of mean t_1/2 for destaining curves shown in panel D. n=149–362 puncta; **p<0.01, ***p<0.001 compared to vehicle (Veh), Mann-Whitney. (F) On withdrawal day 10 following repeated METH, AMPH in vitro induced PPP while AMPH in combination with SULP normalized release. (G) Following repeated METH, AMPH in vitro induced PPP over 140 days of withdrawal while AMPH in combination with SULP normalized release. n=167–368 puncta for each condition; *p<0.05, **p<0.01 compared to Veh from the same withdrawal day, Mann-Whitney.