Fig. 2: Cocaine exposure potentiates GABAergic inputs onto DMS CINs.
From: Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons
a Confocal images of cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) in a ChAT-eGFP mouse. b–e Repeated cocaine (Coc, blue) but not saline (Sal, black) intraperitoneal (i.p.) injections reduced the spontaneous firing frequency (freq.) of DMS CINs 2 d after the last injection; *p = 0.0328. f Cocaine-induced inhibition of DMS CIN activity persisted 24 d after the last injection; *p = 0.0257. g–i, Sample spontaneous IPSCs (sIPSCs) traces (g). Cocaine increased the frequency (h; *p = 0.0337), but not amplitude (amp.) (i), of sIPSCs in DMS CINs. j, k Cocaine decreased paired-pulse ratios (PPR) of electrically evoked IPSCs (eIPSCs) in CINs; *p < 0.05, **p < 0.01, ***p < 0.001 versus Coc; ###p < 0.001. l ChAT-eGFP mice were trained with cocaine intravenous self-administration (IVSA) for 7 d; DMS CINs were recorded 10 d after the last training session. m, Cocaine IVSA inhibited DMS CIN firing 10 d after the last exposure; **p = 0.003. n, o Cocaine IVSA increased the frequency (n; **p = 0.006), but not amplitude (o), of sIPSCs. p, q Cocaine IVSA potentiated eIPSCs in DMS CINs; ***p < 0.001 versus Sal, ###p < 0.001. r Cocaine IVSA decreased the eIPSC PPR in DMS CINs; **p = 0.002. Sti.: Stimulation, n.s. (not significant; i, o). Unpaired t test (e, f, h, i, m, n, o, r), two-way RM ANOVA followed by Tukey post-hoc test (k, q). n = 11 neurons from 3 mice (11/3) (e, Sal), 10/3 (e, Coc; f, Sal), 11/4 (f, Coc), 18/4 (h, i; Sal), 20/4 (h, i; Coc), 26/3 (k, Sal), 23/3 (k, Coc), 12/4 (m, Sal), 14/4 (m, Coc), 13/4 (n, o; Sal), 17/4 (n, o, Coc), 9/4 (q, Sal & Coc; r, Sal & Coc). Data are presented as mean values ± SEM. Source data are provided as a Source Data file.
