Figure 1.

Cue-induced increases in extracellular glutamate are antagonized by stimulating mGluR2/3, but not by blocking mGluR5. A, Self-administration and extinction lever pressing for all rats used in the microdialysis studies. Arrow indicates switch from 10 d of self-administration to 14 d of extinction training. B, Histological localization of the active dialysis membrane in the NAcore, which often traversed striatal areas dorsal or ventral to NAcore. C, Cue presentation increased extracellular glutamate significantly in the NAcore. The increase in glutamate was abolished by introducing the mGluR2/3 agonist LY379268 (100 μm), but not the mGluR5 negative allosteric modulator MTEP (100 μm) 40 min before initiating cued reinstatement. Data are shown as the percentage change from the average baseline value (0–80 min). n in each group is shown in bars in D. D, Reverse microdialysis of either LY379268 or MTEP prevented cue-induced reinstatement. Conditioned cues were restored to active lever presses in all groups except the extinction group. n is shown in bars and is the same for C and D. All data shown as mean ± SEM. *p < 0.05, compared with extinction using a Sidak test for multiple comparisons; +p < 0.05 comparing cue with MTEP.