TYROSINE DEPLETION, MOOD AND COGNITION IN HEALTHY HUMAN SUBJECTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Brain chemicals allow all forms of behavior to take place, including problem solving, emotion, and future directed actions. One chemical that is of interest to neuroscientists is dopamine, which is present throughout the brain but which is thought to play a special role in facilitating reward-directed behavior and in facilitating working memory. Working memory is when you hold information in mind while working toward some future action. Importantly, dopamine appears to facilitate this process. In clinical conditions where dopamine activity is impaired, goal-directed behavior is deficient. Examples include schizophrenia, Parkinson's disease, and phenylketonuria. Part of understanding these clinical conditions is to understand how the dopamine system functions in healthy people. This is difficult, because we would like to study the system without actually going into the brain or introducing a manipulation that is particulary intensive. One new method for studying dopamine activity outside of hospital laboratories is referred to as "tyrosine depletion". Acute tyrosine depletion involves the one-time ingestion of a protein mixture that is deficient in the proteins that are involved in dopamine synthesis. Those proteins are tyrosine and phenylalanine. In this study, we will use tyrosine depletion to lower dopamine activity in healthy people, measuring aspects of their behavior in response. We hypothesize that the transient lowering of activity within the brain's dopamine system will subtly (significantly) impair working memory and responsivity to rewarding stimuli. Healthy adults will be tested in a between-subjects design. Each will make one outpatient visit to the GCRC. The visit will last for approximately seven hours. During this time, a protein drink will be ingested that is either (a) balanced in large amino acid proteins (b) deficient in tyrosine + phenylalanine. Five hours after drink ingestion, cognitive processing will be tested through a battery of tasks designed to measure working memory. The amino acids will be purchsaed in powdered form by the PI and stored for the duration of the study in the GCRC. The PI will also provide all equipment necessary to conduct cognitive testing. GCRC resources are requested to prepare the amino acid mixtures and to monitor partipants' vital signs after drink ingestion.