Noradrenergic effects in tardive dyskinesia, akathisia and pseudoparkinsonism via the limbic system and basal ganglia.

1. This paper proposes that the neuropsychiatric symptoms of tardive dyskinesia, akathisia and pseudoparkinsonian tremor are modulated by a noradrenergic pathway that projects from the locus coeruleus to the limbic system. 2. The proposed pathway is found to the consistent with neuroanatomical and neurochemical data in the literature. 3. The proposed pathway is found to be clinically consistent with observations by ourselves and others on the efficacy of clonidine and beta-adrenoreceptor blockers like propranolol for treating akathisia and pseudoparkinsonian tremor. It is also consistent with reports by ourselves and others that some patients with tardive dyskinesia benefit from treatment with propranolol or clonidine. 4. Noradrenergic modulation of the limbic system by way of the locus coeruleus accounts for a number of clinical observations, such as the worsening of tardive dyskinesia by stress, the greater risk for tardive dyskinesia in patients with affective disorder, the time-of-onset of tardive dyskinesia, and the coexistence of tardive dyskinesia and pseudoparkinsonism. 5. The functional significance of beta-adrenoreceptors in the basal ganglia is considered from an evolutionary perspective. 6. The model proposed in this article appears to have considerable heuristic value because it may further our understanding of Gilles de la Tourette syndrome and attention deficit disorder (hyperkinesis).