Delayed regional metabolic actions of phencyclidine.

Phencyclidine (PCP), a psychotomimetic drug of abuse, produces mental changes and manifestations in humans which are reminiscent of schizophrenia, though the mechanism of these actions remains unknown. We report here a biphasic time course of PCP action on regional cerebral glucose metabolism extending over 48 h. A single dose of PCP (8.

PET-FDG test-retest reliability during a visual discrimination task in schizophrenia.

Objective: Reliability of assessment is important in any kind of neuropsychiatric study, but is particularly pivotal in schizophrenia research where symptom instability is common.

Materials And Methods: Two fluorodeoxyglucose PET scans, 1 week apart, were carried out in schizophrenic patients while they were performing a simple visual discrimination task. Subject and scan conditions were held constant.

Low dose raclopride spares the extrapyramidal system in rat brain from metabolic effects.

The effect of a highly selective dopamine D2 receptor antagonist, raclopride ((-)-(S)-3,5-dichloro-N-(1-ethyl-2-pyrrolidinyl) methyl-6-methoxysalicylamide tartrate), on regional cerebral glucose metabolism in rat brain was determined using [14C]2-deoxyglucose autoradiography, and compared to a typical neuroleptic, haloperidol. Based on preclinical biochemistry and early clinical trial reports, it was hypothesized that raclopride would fail to functionally affect brain regions putatively involved with motor function, while altering psychosis-related regions. Raclopride at a low dose (1.

Pharmacologic relationship of antisaccade and dyskinesia in schizophrenic patients.

Abnormalities in saccadic eye movements have been found in schizophrenics with tardive dyskinesia (TD). This finding supports accumulating evidence for a GABAergic dysfunction in the subcortical-cortical circuits controlling motor and oculomotor behavior. We found that in response to muscimol, a direct-acting GABA agonist, changes in the antisaccade error rate and dyskinesia score were strongly correlated.

Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients.

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found.

GABA agonist-induced changes in motor, oculomotor, and attention measures correlate in schizophrenics with tardive dyskinesia.

Saccadic distractibility, Stroop color-word scores, and serial dyskinesia assessments were obtained on 10 schizophrenic patients with tardive dyskinesia during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct-acting GABA agonist. Although no significant difference in the measures was evident between conditions, a significant correlation was found between GABA agonist-induced changes in saccadic distractibility and dyskinesia scores where no correlation existed between these measures on placebo. Improvement in saccadic distractibility was also correlated with reduction in attention performance, as measured by Stroop.

Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome.

A hypothesis of psychosis localization in schizophrenia was derived from studying metabolic alterations in rat brain in response to phencyclidine hydrochloride administration. Since phencyclidine and its selective agonist dizocilpine maleate (MK801) induced overlapping and long-lasting metabolic alterations predominantly in limbic areas, the hypothesis developed that schizophrenic patients with psychosis would evidence functional abnormalities in limbic circuits compared with normal controls. Accordingly, 12 actively psychotic, drug-free patients with schizophrenia and matched normal controls underwent functional brain scans using positron emission tomography and fluorodeoxyglucose.

Co-administration of progabide inhibits haloperidol-induced oral dyskinesias in rats.

Vacuous chewing movements in rats may be an animal analogue of the human motor disorder, tardive dyskinesia. The movements are phenomenologically and pharmacologically similar to tardive dyskinesia. The pathophysiology of these involuntary oral movements, and perhaps of tardive dyskinesia, are likely to include both dopamine receptor changes, and alterations in GABA (gamma-aminobutyric acid) system function.

Pharmacologic properties of (-)-3PPP (preclamol) in man.

The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar "rising dose" placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo.

Expression of acidic and basic fibroblast growth factors in the substantia nigra of rat, monkey, and human.

The distribution of acidic (aFGF) and basic (bFGF) fibroblast growth factor mRNA and protein were examined in mesencephalon by immunohistochemistry, immunoblot analysis, in situ hybridization histochemistry, and RNA analysis. Coexistence of aFGF or bFGF with tyrosine hydroxylase protein in nigral cells was observed with immunohistochemistry. Both aFGF and bFGF mRNAs were found in the substantia nigra.

Tobacco smoking increases square-wave jerks during pursuit eye movements.

Smooth-pursuit eye-movement (SPEM) abnormalities have been consistently observed in schizophrenia. The SPEM changes in schizophrenia are not thought to be an artifact of voluntary attention or medication, although a number of nondisease factors are known to affect SPEM. However, cigarette smoking has recently been reported to deteriorate SPEM in both smokers and nonsmokers.

Sleep polygraphy in schizophrenia: methodological issues.

The findings of sleep studies in schizophrenia have remained inconsistent in the literature as exemplified by the recent controversy regarding reduced rapid eye movements (REM) latency in these patients. These inconsistencies can partly be explained by major methodological shortcomings in studies evaluating sleep in schizophrenia. Lack of standardized scoring and diagnostic methods in the earlier studies and more recently, the effect of neuroleptic treatment or its withdrawal, have confounded the sleep results.

Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy.

Because of the efficacy of specific gamma-aminobutyric acid (GABA) agonists in tardive dyskinesia, the authors tested the benzodiazepine clonazepam in a 12-week, double-blind, placebo-controlled, randomized crossover trial in 19 chronically ill patients with tardive dyskinesia who were being treated with neuroleptics. They found a 35% decrease in dyskinesia ratings with clonazepam treatment. The six patients with predominantly dystonic symptoms showed greater benefit than the 13 patients with predominantly choreoathetoid dyskinesias.

Neuroleptic-induced vacuous chewing movements as an animal model of tardive dyskinesia: a study in three rat strains.

Vacuous chewing movements (VCMs) in three different rat strains developed at considerably different rates after 19 weeks of continual haloperidol treatment at an average daily dose of 1.5 mg/kg. Sprague Dawley (SD) rats displayed relatively high rates of VCMs with low variability, compared to Wistar (W) and Long Evan (LE) rats.

Effect of neuroleptic withdrawal on plasma prolactin: a possible marker of receptor adaptation.

Stable schizophrenic and schizoaffective outpatients underwent abrupt withdrawal from a fixed dose of neuroleptic. Prolactin concentrations were determined preceding and following drug withdrawal. Basal prolactin concentrations were significantly lower 3, 4, or 5 days following drug withdrawal than on subsequent days.

Oculomotor abnormalities and their clinical correlates in schizophrenia.

Smooth pursuit eye movements (SPEMs) have been consistently found to be abnormal in the majority of schizophrenic patients. The traditional SPEM measurement technique, however, fails to inform us about the underlying oculomotor deficit in these patients, since it remains a non-specific and a global oculomotor measure. A number of diverse clinical features such as tardive dyskinesia (TD) or negative symptoms correlate with the SPEM abnormality.

Alterations in sleep polygraphy after neuroleptic withdrawal: a putative supersensitive dopaminergic mechanism.

Although a number of studies have reported sleep disturbances following neuroleptic withdrawal, a full description of such changes in sleep architecture is not available. Polysomnographic, plasma prolactin, and clinical measurements were carried out in a small number of patients on chronic neuroleptic treatment and after drug withdrawal. Preliminary findings show that in these chronically treated schizophrenic patients with and without tardive dyskinesia (TD), abrupt neuroleptic withdrawal induces reductions in total sleep, rapid eye movement (REM) sleep, and plasma prolactin.

Increased saccadic distractibility in tardive dyskinesia: functional evidence for subcortical GABA dysfunction.

In mammals, GABAergic projections from the substantia nigra reticulata to the superior colliculus provide tonic inhibition to tectal neurons involved in the generation of saccades. Dysfunction of this pathway has been shown to produce saccadic "distractibility" in the experimental monkey. In two oculomotor paradigms, control of saccadic eye movements was tested in chronic schizophrenic patients with (n = 18) and without (n = 16) tardive dyskinesia (TD) and normal controls (n = 8).

Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia.

The concentration of the endogenous excitotoxin quinolinic acid was determined in the cerebrospinal fluid of drug-free patients suffering from Huntington's disease or schizophrenia (control group). In both diseases, quinolinic acid concentrations were highly variable (less than 4-48 nM) but the mean levels for each disease group were not significantly different from each other or from the quinolinic acid concentration of normal cerebrospinal fluid. Analysis of steady-state cerebrospinal fluid quinolinic acid concentration is unlikely to be of value as a diagnostic tool in Huntington's disease.