The PET imaging technique is one of a few available techniques that allow insight into the living brain, andPET using rat models has become an important tool in neuroscience. The Rat Conscious Animal PET scanner(RatCAP) is unique among small-animal PET scanners in that it eliminates the need for general anesthesia,and thus permits imaging of dynamic changes in brain activity while the animal experiences and acts on theenvironment. This is made possible by the scanner's miniature size which allows for direct attachment to therat's head and significant freedom of movement. The overarching goal of this proposal is to explore thefeasibility of using different PET radiotracers to assess acute changes in brain chemistry in the behaving rat.This is a critical step in bringing Brookhaven's mature RatCAP technology, developed over 8 years ofDepartment of Energy support but no longer funded, into routine use in preclinical neuroscience. Specifically,we will experiment with three carbon-11 radiotracers: 11C-raclopride, an antagonist for dopamine D2 receptors(D2), 11C-(+)-PHNO, an agonist which binds specifically to the high affinity state of D2, and 11C-CNS-5161, anactivity-dependent tracer which binds to NMDA receptors.
Specific Aim 1 is to develop the 'bolus + infusion'radiotracer administration technique, which will maintain a steady-state condition of the tracer in the brain anddetect perturbations from equilibrium.
Specific Aim 2 is to test the radiotracers for their potential to reflectperturbations from equilibrium that are brought about by interventions with psychoactive drugs, including drugsof abuse.
Specific Aim 3 is to use the 'bolus + infusion' technique to correlate changes in radiotracerequilibrium with changes in the behavior of rats that engage in sexual interactions. We hope that this proposalwill result in the generation of first data that will mark the beginning of a new approach in the field ofneuroscience. We envision that these data will allow for the formation of novel and specific hypothesesregarding the effects of natural and drug rewards on the brain that will then form the basis for long-termprojects.1
to human health The PET imaging technique is one of a few available techniques that allow insight into the living brain and is of major importance for the study of mental health in humans and animal models of human disease states. The development of the RatCAP tomograph represents a groundbreaking tool in the neurosciences, since for the first time it permits PET imaging in behaving animals and, thus, exceeds in some ways the possibilities of human imaging. The protocols we intend to develop in this proposal for use with the RatCAP may lead to new discoveries related to the effects of drugs of abuse and natural rewards on brain and behavior. 1
| Gold, Maria E L; Norell, Mark A; Budassi, Michael et al. (2018) Rapid 18F-FDG Uptake in Brain of Awake, Behaving Rat and Anesthetized Chicken has Implications for Behavioral PET Studies in Species With High Metabolisms. Front Behav Neurosci 12:115 |
| Schulz, Daniela; Henn, Fritz A; Petri, David et al. (2016) Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl. Neuroscience 329:83-92 |
| Gold, Maria Eugenia Leone; Schulz, Daniela; Budassi, Michael et al. (2016) Flying starlings, PET and the evolution of volant dinosaurs. Curr Biol 26:R265-7 |
| Huston, Joseph P; Silva, Maria A de Souza; Komorowski, Mara et al. (2013) Animal models of extinction-induced depression: loss of reward and its consequences. Neurosci Biobehav Rev 37:2059-70 |
