Summary: Tourette’s Syndrome is commonly treated with two very different classes of drugs, haloperidol and clonidine. Although both drugs are effective in the treatment of TS, these two pharmacological agents have been shown to interact with two distinct chemically-defined neuronal systems. Haloperidol is known to block the actions of dopamine (DA), the chemical messenger (termed neurotransmitter) utilized by certain midbrain neurons. In contrast, clonidine acts to reduce the activity of neurons in brain stem structure known as the locus coeruleus; these neurons utilize the neurotransmitter norepinephrine (NE). In order to gain a better understanding of the brain mechanisms which may be involved in TS, it is important to define the system or systems within the brain which may mediate the therapeutic effects of either haloperidol or clonidine, and in particular to ascertain if there is a single brain circuit involved in TS or, alternatively, multiple systems which may be affected. To this end, we are attempting to look at the interaction of DA and NE neurons in the brain, both from the standpoint of anatomical studies directed at demonstrated neuronal circuits linking DA and NE neurons, and in terms of biochemical experiments which attempt to ascertain if changes in the activity of certain DA neurons result in functional changes in the activity of NE-containing neurons. Our preliminary date suggests that a single common brain circuit, involving multiple neurotransmitter substances, may be involved in TS. Identification of the sites of interaction of the two chemical (DA and NE) neurotransmitter systems involved in TS may help to identify more specific and effective treatments for TS. Dr. Ariel Y. Deutch, Dr. Robert H. Roth Yale University School of Medicine, New Haven, CT Award: $14,817 Tourette Association of America, Inc.. – Research Grant Award 1985