Modulation of neurotransmitter efflux in insular cortex following virus-mediated gene transfer and presentation of an entrained palatable food stimulus (darkness/food). A. (left) Young control (YC) rats showed a robust cholinergic response to presentation of the food stimulus that peaked during the second post-stimulus collection. This effect was abolished in aged control (AC) rats and young animals treated with preproorexin antisense (YAS). While there was a trend for preproorexin sense treatment to restore a response to the food stimulus in aged rats (AS), this did not reach significance. (right) Neither age nor virus treatment altered basal ACh levels insular cortex. ***p < 0.001 vs. baseline. B. (left) Following presentation of the food stimulus, YC rats showed a gradual increase in insular cortex glutamate levels that peaked and reached statistical significance during the final post-stimulus collection. (right) Treatment with preproorexin sense virus increased basal glutamate levels in insular cortex of AS rats relative to all other ages and treatment conditions. *p < 0.05 vs. baseline. C. (left) Presentation of the food stimulus was associated with a delayed increase in insular cortex GABA efflux in YC rats that reached significance only during the eighth collection (fourth post-stimulus collection). (right) Similar to glutamate, AS rats showed significant elevations in basal GABA levels in insular cortex relative to the other treatment conditions. *p < 0.05 vs. baseline. D. Representative histochemical verification of microdialysis probe placement. The probe tract typically extended through deeper layers of granular (GIC) and dysgranular (DIC) subdivisions of insular cortex at a level corresponding to roughly Bregma + 1.0 mm (inset; (Paxinos and Watson, 1998)) and had its greatest length in agranular insular cortex (AIC). Other abbreviations: CPu, caudate-putamen; Cl, claustrum. Scale bar, approximately 1.0 mm. Group sizes: N = 7–10 (AC), N = 6 (AS), N = 7–9 (YC), N = 7–8 (YAS).