Fig. 4. Restraint stress produces persistent changes in negative-affective-like states that are not present under basal conditions.

a Following adolescent vapor exposure, mice were allowed to rest until adulthood before being exposed to the open field. Protracted AIE withdrawal did not alter anxiety-like activity in the open field in females (Ai) or males (Aii). In the NIH task, mice were exposed to 1 h of restraint stress or kept in their home cage. AIE-exposed females (Bi), but not males (Bii), exposed to restraint stress significantly enhanced their latency to consume an appetitive reinforcer compared to their air counterparts, ns = 6–8 in females and 7–10 in males. To observe whether mGlu5 receptors mediate this behavior in female mice, vehicle or 30 mg/kg MTEP was injected 30 min prior to restraint stress (Biii). MTEP administration blocked stress-induced enhancements in latency to consume, ns = 7–11. Data are shown as mean ± SEM. Significant main effect at ^^p < 0.01 and ^^^p < 0.001. Significantly different than the respective control at *p < 0.05.