Figure 4.

Daily N-acetylcysteine prevents long-term changes in extracellular glutamate levels in the nucleus accumbens produced by repeated cocaine. a, b, Basal glutamate levels (mean ± SEM) are depicted as picomoles per microliter across 20 min samples (a) or area under the curve calculated using samples collected before the cocaine injection (b). c, d, Cocaine-evoked glutamate is presented as percent change from baseline (c) or area under the curve calculated using samples collected after the cocaine injection (d). Group designations refer only to treatments given during self-administration training, at which time rats received saline or N-acetylcysteine (60 mg/kg, i.p.) before self-administering saline or cocaine (0.5 mg/kg, i.v./infusion; 2 h/d). The pretreatment/self-administration drug assignments resulted in four groups: Sal–Sal (N = 14), NAC–Sal (N = 6), Sal–Coc (N = 14), and NAC–Coc (N = 7). Seven days after the last self-administration session, rats underwent daily extinction training in the absence of any drug treatments. Microdialysis was then used to sample extracellular glutamate before and after an acute cocaine challenge (10 mg/kg, i.p.) in the absence of N-acetylcysteine. *Significant difference from Sal–Sal controls; Dunnett's t, p < 0.05. ⁺Significant difference from the last baseline sample; Dunnett's t, p < 0.05. ^#Significant difference from NAC–Coc rats (c); Dunnett's t, p < 0.05.