Jack E. Rosenblatt

A probable neuroleptic effect on platelet monoamine oxidase in chronic schizophrenic patients

Platelet monoamine oxidase activity (MAO) was studied serially over time in 16 chronic schizophrenic patients when medication free and then when medicated. Thirteen of the 16 patients had significant decreases in platelet MAO activity following neuroleptic drug treatment. The change in MAO activity was found to be correlated with response to treatment and to dose of medication.

A biochemical study of tardive dyskinesia in young male patients.

Based on specific criteria, tardive dyskinesia was diagnosed in 6 out of 29 young schizophrenic male inpatients. We compared several biochemical parameters in these six dyskinesia patients with those in six matched controls. The patients with dyskinesia had significantly lower platelet monoamine oxidase activity and significantly higher plasma dopamine-beta-hydroxylase activity as compared with the controls, thus confirming our previous findings in a population of elderly female inpatients. The dyskinetic and nondyskinetic groups did not differ from each other in mean whole blood serotonin concentration and mean serum neuroleptic concentration as measured with a radioreceptor binding assay. Possible significance of our results is discussed.

POSTMORTEM NEUROCHEMICAL STUDIES IN CHRONIC SCHIZOPHRENIA

ABSTRACT Catecholamines and some of their metabolites were measured in brain regions from autopsied chronic schizophrenics and controls. No significant changes in dopamine or its metabolites were found. Norepinephrine concentrations were increased in the nucleus accumbens of chronic paranoid schizophrenics relative to chronic undifferentiated schizophrenics, other psychiatric patients and normals. Conjugated 3-methoxy, 4-hydroxyphenylglycol (MHPG) was also increased in paranoid schizophrenics in the nucleus accumbens relative to normals. Increased norepinephrine and free MHPG in the hypothalamus of schizophrenics were found in comparison with normals. Increased tritiated (3H) neuroleptic binding was found in schizophrenic caudate nuclei relative to normals. No other differences between patients and controls in other binding sites or between schizophrenic sub-types were demonstrated. Endogenous peptides (methionine-enkephalin, substance P, and neurotensin) were measured in several brain regions. In a small number of chronic undifferentiated schizophrenic patients, methionine-enkephalin and substance P concentrations in caudate nuclei were increased relative to chronic paranoid schizophrenics and normals. The number of subjects and pre-and postmortem variables, such as neuroleptic treatment and the difficulties inherent in sub-typing deceased patients, warrant cautious interpretations of the significance of these findings. Nevertheless, sub-typing chronic schizophrenia by phenomenology may yield more homogenous groups while providing a means for controlling treatment variables.

Interactions of amphetamine, pimozide, and lithium on plasma norepinephrine and dopamine-beta- hydroxylase in schizophrenic patients

The peripheral interactions of amphetamine with antipsychotic agents may elucidate some central mechanisms by which these drugs affect the behavioral responses to amphetamine. The authors studied the effects of intravenous amphetamine on plasma levels of norepinephrine (NE), dopamine-beta-hydroxylase (DBH), pulse rate, and blood pressure in schizophrenic patients. Amphetamine increased plasma NE, pulse rate, and blood pressure without significantly changing plasma DBH. DBH activity was similar in drug-free schizophrenic and normal subjects. Neither pimozide nor lithium altered these amphetamine effects nor changed any of the cardiovascular parameters measured in the drug-free subjects. Pimozide and lithium alter behavior and the behavioral effects of amphetamine, but neurotransmitters other than NE may be involved.

Increased renal neuroleptic binding in spontaneously hypertensive rats

The present experiments demonstrate high affinity stereospecific binding of the dopaminergic ligand [3H]spiroperidol to rat renal membranes. The binding was saturable, regionally distributed, and showed the same specificity as the caudate [3H]spiroperidol site for displacement by dopaminergic antagonists. Since there is an association between hypertension and abnormalities of renal blood flow, which appears to be regulated in part by dopamine, [3H]spiroperidol binding was measured in kidneys of spontaneously hypertensive rats. In two independent experiments renal cortical [3H]spiroperidol stereospecific binding was increased in spontaneously hypertensive rats.

CATECHOLAMINE RECEPTOR STABILIZATION: A POSSIBLE MODE OF LITHIUM'S ANTI-MANIC ACTION

ABSTRACT Chronic administration of lithium to rats treated with repeated doses of haloperidol prevents the dopamine receptor supersensitivity that normally develops when haloperidol is administered alone. Lithiums prevention of dopamine receptor supersensitivity has been documented by behavioral, neurophysiological, and biochemical receptor binding techniques. Chronic lithium treatment alone in rats has small but reproducible effects: an increase in α-receptor binding, a decrease in β-receptor binding and no alteration in dopamine receptor binding. In preliminary experiments, lithium is able to block the development of the α- and β-receptor sensitivity that normally accompanies brain norepinephrine depletion by 6-hydroxydopamine.