A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation.

UNLABELLED: To reduce imaging costs, we designed a head holder for scanning two rats simultaneously in small animal PET scanners. Our goals were (i) to maintain high sensitivity and (ii) to minimize repositioning error between scans. METHODS: A semi-stereotaxic dual rat head holder was designed and constructed for dual rat scanning in our IndyPET-II scanner and the commercial microPET P4. It was also used for single rat scanning in a small-bore, high-resolution animal scanner ("ISAP"). Positional repeatability was validated via multiple [11C]Raclopride scans of a single rat on different days. Accuracy of repositioning was determined by visual comparison of images, and by metrics derived through image alignment. Kinetic validation was assessed via analysis of [18F]Fluorodeoxyglucose ([18F]FDG) dynamic PET studies of six rats. Each rat was scanned twice: once individually, with brain positioned at the center of field of view (CFOV), and once with a partner, with brain away from CFOV. Both rats were injected with FDG during each dual rat session. Patlak uptake constants (Ki) were calculated from whole brain images. Effects of attenuation and scatter correction on single versus dual scan images were explored. RESULTS: Image comparison and alignment metrics indicated excellent repositioning of rats. Scaled time-activity-curves from single and dual rat scans were indistinguishable. Average single and dual scan Ki values differed by only 6.3+/-7.5%. CONCLUSION: Dual rat scanning in a semi-stereotaxic holder is practical for economical small animal scanning and does not compromise kinetic accuracy of [18F]FDG dynamic scan data.

When what you see isn't what you get: alcohol cues, alcohol administration, prediction error, and human striatal dopamine.

BACKGROUND: The mesolimbic dopamine (DA) system is implicated in the development and maintenance of alcohol drinking; however, the exact mechanisms by which DA regulates human alcohol consumption are unclear. This study assessed the distinct effects of alcohol-related cues and alcohol administration on striatal DA release in healthy humans. METHODS: Subjects underwent 3 PET scans with [(11)C]raclopride (RAC). Subjects were informed that they would receive either an IV Ringer's lactate infusion or an alcohol (EtOH) infusion during scanning, with naturalistic visual and olfactory cues indicating which infusion would occur. Scans were acquired in the following sequence: (1) Baseline Scan: Neutral cues predicting a Ringer's lactate infusion, (2) CUES Scan: Alcohol-related cues predicting alcohol infusion in a Ringer's lactate solution, but with alcohol infusion after scanning to isolate the effects of cues, and (3) EtOH Scan: Neutral cues predicting Ringer's, but with alcohol infusion during scanning (to isolate the effects of alcohol without confounding expectation or craving). RESULTS: Relative to baseline, striatal DA concentration decreased during CUES, but increased during EtOH. CONCLUSION: While the results appear inconsistent with some animal experiments showing dopaminergic responses to alcohol's conditioned cues, they can be understood in the context of the hypothesized role of the striatum in reward prediction error, and of animal studies showing that midbrain dopamine neurons decrease and increase firing rates during negative and positive prediction errors, respectively. We believe that our data are the first in humans to demonstrate such changes in striatal DA during reward prediction error.

Heterogeneous effects of alcohol on dopamine release in the striatum: a PET study.

BACKGROUND: A dopaminergic response to alcohol in humans has not been demonstrated consistently with positron emission tomography (PET). We hypothesized that the effect of alcohol on striatal dopamine (DA) release may be anatomically heterogeneous between subjects. Our approach was to identify voxels that exhibited alcohol-induced DA responses within the striatum, and to determine the relationships between DA responses and alcohol-related behavior. METHODS: A novel method was developed to examine the anatomic extent and magnitude of striatal DA responses to alcohol across subjects. Thirteen healthy control subjects underwent 2 PET scans with [11C]raclopride (1 at baseline, 1 with an i.v. alcohol infusion to a target breath alcohol concentration of either 60 or 80 mg%). Parametric images of striatal binding potential (BP) were used to create maps of change in BP (deltaBP, an index of changes in DA levels). The anatomic extent and magnitude of DA responses were determined with voxel extraction methods. Subjective responses ("High," "Intoxication") to the alcohol infusion and behavioral data from the 90-day time-line follow back were assessed for relationships with DA responses to alcohol. RESULTS: A voxel-wise t-test between baseline and alcohol BP images did not show any differences in D2/D3 receptor availability between the conditions. Data from the striatal deltaBP maps nevertheless showed that the anatomic extent and magnitude of alcohol-induced DA release in the striatum are correlated with subjective responses to alcohol. CONCLUSIONS: The heterogeneity of dopaminergic responses to alcohol across subjects may be a reason for the lack of reports demonstrating DA involvement in alcohol-related behaviors. By allowing for different spatial patterns of DA release within each subject's striata, we showed correlations between alcohol-induced DA release in the striata and behavioral outcomes related to alcohol.