Abstract
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Objectives: We employed a novel paradigm that combines PET imaging with behavioral challenges in awake, freely moving rats to test the hypothesis that exposure to drug-paired environmental cues decreases striatal 11C-raclopride (11C-rac) binding in a behavioral model of cue-induced reward (Conditioned Place Preference).
Methods: Male rats (n=10) were alternately paired with COC (5 mg/kg, iv) or vehicle (VEH) in distinct environments for 20 days. Preference was assessed 24 h after the final pairing session in a drug-free state. Awake rats received two 11C-rac scans, each randomized to the COC- or VEH-paired environments. 25 min of uptake was followed by light anesthesia and a 25 min microPET acquisition. The ratio of striatal (STR) to cerebellar radioactivity was used as an index of binding potential (BP). The difference in BP from the COC- or VEH-paired cues was used to assess the effects of environmental cue on 11C-rac binding and thus, on dopamine (DA) release.
Results: ROI analyses confirmed a decrease in STR 11C-rac BP during exposure to COC-paired cues versus exposure to VEH-paired cues (F[1,16]=4.56, p<0.05) and (F[1,16]=12.24, p<0.003) in ventral and dorsal STR, respectively (Figure 1a). Preference for the COC-paired environment correlated with COC-induced changes in 11C-rac BP in the ventral STR (r=0.87; p<0.003, figure 1b). Thus, rats that strongly preferred the COC-paired environment had larger decreases in 11C-rac binding compared to rats with weak preferences.
Conclusions: Exposure to COC-paired environment significantly decreases 11C-rac binding in conditioned rats. These PET studies in freely moving animals provide the first evidence that PET and a host of new radiotracers can be used to capture dynamic molecular events in behaving animals.
Research Support: DOE OBER and NIH
- Society of Nuclear Medicine, Inc.