RATIONALE: The noradrenaline (NA) system is implicated in neurodegenerative and psychiatric disorders; however, our understanding is impaired by the lack of well-validated radioligands to assess NA function and release. Yohimbine, an α2 adrenoceptor antagonist, has recently been developed as a carbon-11 [11C]-labeled radioligand for positron emission tomography (PET) imaging studies. OBJECTIVES: Here we explore the hypothesis that yohimbine can be used as an in vivo tracer of NA receptor binding and release during amphetamine challenges in Landrace pigs. METHODS: Pigs underwent baseline PET scans with [11C]yohimbine and were then challenged with 10 mg/kg d-amphetamine 20 min prior to a second [11C]yohimbine scan. Using the Logan analysis model, volumes of distribution were calculated from fits of the kinetic data 25-90 min post-yohimbine injection. RESULTS: Amphetamine decreased [11C]yohimbine volume of distribution in the brain regions under investigation, including the thalamus, caudate nucleus, and cortical regions. CONCLUSION: These data suggest that the binding of [11C]yohimbine to α2 adrenoceptors may be displaceable by increases in synaptic concentrations of the endogenous ligand, NA, and possibly dopamine, suggesting the possibility that [11C]yohimbine may be used as a surrogate marker of NA release in vivo.