Lewy Body Disease Patients Research Articles

Serotonin-dopamine interaction and its relevance to schizophrenia.

The therapeutic success of clozapine and risperidone has focused attention on the interaction between serotonin and dopamine systems as an avenue for superior therapeutics in schizophrenia. The authors review the neurobiological basis for this interaction and its clinical relevance. The authors synthesized information from more than 100 published articles obtained through electronic and bibliography-directed searches. The serotonin system inhibits dopaminergic function at the level of the origin of the dopamine system in the midbrain as well as at the terminal dopaminergic fields in the forebrain. Serotonergic antagonists release the dopamine system from this inhibition. This disinhibition of the dopamine system in the striatum may alleviate neuroleptic-induced extrapyramidal symptoms, and a similar disinhibition in the prefrontal cortex may ameliorate negative symptoms. However, the benefits of combined serotonergic-dopaminergic blockade may be observed in only a narrow dose range and may be lost with doses that produce suprathreshold dopaminergic blockade. Serotonergic modulation of dopaminergic function provides a viable mechanism for enhancing therapeutics in schizophrenia, but much remains unclear. Future research will have to establish the existence of this interaction in humans in vivo, specify the conditions under which it leads to optimal therapeutic benefits, and explore the possibility of using specific serotonergic treatments as flexible adjuncts to typical neuroleptics, rather than the present trend toward using single drugs with combined actions.

Alterations in peptide levels in Parkinson's disease and incidental Lewy body disease.

The levels of the neuropeptides Met- and Leu-enkephalin (MET-ENK, LEU-ENK), substance P and neurotensin were measured by a combined high performance liquid chromatography/radioimmunoassay (HPLC/RIA) method in postmortem samples of basal ganglia from Parkinson's disease patients, incidental Lewy body disease patients (pre-symptomatic Parkinson's disease) and matched controls. Dopamine (DA) levels were reduced in the caudate nucleus and putamen in Parkinson's disease, but unaltered in incidental Lewy body disease. The levels of MET-ENK were reduced in the caudate nucleus, putamen and substantia nigra in Parkinson's disease. Met-enkephalin levels were reduced in the caudate nucleus and in the putamen in incidental Lewy body disease. Leu-enkephalin levels were decreased in the putamen and were undetectable in the substantia nigra in Parkinson's disease. Leu-enkephalin levels were unchanged in incidental Lewy body disease, although there was a tendency to a reduction in putamen. Substance P levels were reduced in the putamen in Parkinson's disease. No significant changes in substance P content were observed in incidental Lewy body disease. Neurotensin levels were increased in the substantia nigra in Parkinson's disease. Neurotensin levels in incidental Lewy body disease were not altered significantly, but tended to parallel the changes in Parkinson's disease. The changes in basal ganglia peptide levels in incidental Lewy body disease generally followed a trend similar to those seen in Parkinson's disease, but were less marked. This suggests that they are an integral part of the pathology of the illness and not secondary to DA neuronal loss or a consequence of prolonged drug therapy.