The factor structure of the Profile of Mood States (POMS) and its relationship to occupational lead exposure.

The Profile of Mood States (POMS) is an instrument composed of six mood scales that were developed using clinical populations. This study examines the replicability of the POMS factor structure in lead-smelter workers and its association with demographic variables and lead exposure. Four hundred sixty-seven current and retired smelter workers completed the POMS, and a factor analysis was performed on the individual items. Two multiple regressions in the currently employed workers (n = 340) with a mean age of 40 years (range, 20-63 years) were used to compare the relationship of the resulting POMS factors with demographic characteristics and two measures of occupational lead exposure: current blood lead level (mean, 28 micrograms/dL; range, 4-62 micrograms/dL) and working-lifetime integrated blood lead level (mean, 711 micrograms-yr/dL; range, 1-1537 micrograms-yr/dL). Factor analysis produced one factor, labeled "general distress," that was composed mainly of items from five of the six POMS subscales (anger, confusion, depression, fatigue, and tension) and a second factor labeled "psychological adjustment." Demographic variables, including education, age, and alcohol use, were significantly related to the "general distress" factor score. After the effects of the demographic variables were accounted for, the "general distress" factor was significantly related to integrated blood lead level but not current blood lead level. Integrated blood lead level, a measure of cumulative lead exposure that included prior high exposure, was significantly related to the POMS "general distress" factor, while a current blood lead level that was relatively low was unrelated. As expected, POMS psychological adjustment was not related to lead exposure. Factor analysis did not support the use of six separate POMS subscales in this occupational population.

Relation of cumulative exposure to inorganic lead and neuropsychological test performance.

OBJECTIVES: To determine if measures reflecting chronic occupational lead exposure are associated with performance on neuropsychological tests. METHOD: 467 Canadian male lead smelter workers (mean (SD) age 43.4 (11.00) years, education 9.8 (3.18) years, years of employment 17.7 (7.43), and current blood lead concentration (B-Pb) 27.5 (8.4) micrograms dl-1) were given a neuropsychological screening battery. Time weighted average (TWA) and time integrated blood levels (IBL) were developed from B-Pb records obtained through regular medical monitoring (mean (range) TWA 40.1 (4.0-66.4) micrograms dl-1, mean IBL 765.2 (0.6-1625.7) micrograms-y dl-1). 14 neuropsychological variables were included in three multivariate analyses of covariance, with each exposure variable as the grouping variable (high, medium, and low) and age, education, score on a measure of depressive symptoms, and self reported alcohol use as the covariates. Groups did not differ in history of neurological conditions. RESULTS: Neither the B-Pb, TWA, nor IBL was significant by multivariate analyses of covariance (MANCOVA). When years of employment, a suppressor variable, was included as a covariate, IBL exposure groups differed significantly on digit symbol, logical memory, Purdue dominant hand, and trails A and B. CONCLUSIONS: A dose-effect relation was found between cumulative exposure (IBL) and neuropsychological performance at a time when current B-Pb concentrations were low and showed no association with performance.

Relationship between bone lead and other indices of lead exposure in smelter workers.

The relationship between blood lead (B-Pb) indices and bone lead was determined in 81 smelter workers. Lead exposure had changed dramatically since the smelter opened 27 years ago; therefore, workers were stratified by years employed. Seventy workers, hired prior to 1979 (Group 1), had a mean (range) age of 46 years (35-64), mean years of employment 23 (16-27), mean years of education 8 (0-13), mean B-Pb 26 micrograms dl-1 (13-43), mean time-weighted average (TWA) B-Pb 44 micrograms dl-1 (23-57) and mean integrated blood lead index (IBL), 983 micrograms Pb year dl-1 (537-1437). Eleven workers, hired after 1978 (Group 2), had a mean age of 34 years (24-55), mean years of employment 11 (5-14), mean years of education 11 (8-12), mean B-Pb 26 micrograms dl-1 (8-13), mean TWA 33 micrograms dl-1 (17-44) and mean IBL 378 micrograms year dl-1 (81-555). Bone lead measured in the mid-tibia used K-X-ray fluorescence. Mean bone lead in Group 1 and Group 2 was 45 (-7-90) and 11 (-12-33) micrograms Pb (g bone mineral)-1, respectively. Linear regression analysis demonstrated a significant relationship between bone lead and B-Pb indices. B-Pb accounted for 10.8%, years employed 12.7%, TWA 31.4% and IBL 36% of the bone lead variance. Using a previously established relationship, the mean bone lead predicted a mean B-Pb content of approximately 8 micrograms dl-1 in Group 1 as compared to 2 micrograms dl-1 in Group 2. The mean B-Pb was 26 micrograms dl-1 in both groups despite differences in contribution from bone stores. Differential contribution of ambient air lead to B-Pb in the two groups of current workers with similar job titles may reflect use of personal protective equipment.

Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens.

Previous studies have demonstrated that several dopamine agonists disrupt sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. Schizophrenic patients also exhibit deficits in PPI when the prepulse precedes the startle stimulus by less than 500 ms. In experiment 1, dopamine (0-40 micrograms) infused directly into the nucleus accumbens in rats caused a dose-dependent decrease in PPI at prepulse intervals shorter than 500 ms. In experiment 2, this effect of accumbens dopamine infusion on sensorimotor gating was found to vary with changes in prepulse intensity. These findings strongly suggest that increased mesolimbic dopamine activity is one substrate of the sensorimotor gating deficits in rats that are caused by treatment with dopamine agonists; similar substrates might mediate deficits in PPI exhibited by schizophrenic patients.

Increases in diversive exploration in rats during hippocampal microinfusions of isoproterenol but not methoxamine.

To test the hypothesis that the increase in locomotor activity and the diversification of stimulus sampling observed during intrahippocampal microinfusions of norepinephrine are mediated by beta adrenergic receptors, rats were infused with either the beta agonist isoproterenol or the alpha-1 agonist methoxamine while being tested in a Behavioral Pattern Monitor. The behavioral profile induced by isoproterenol was qualitatively similar to that observed previously with norepinephrine. Methoxamine had no significant effects. The ability of isoproterenol to mimic the norepinephrine-induced blockade of the hyperactivity associated with intrahippocampal microinfusions of the cholinergic agonist carbachol was also tested. Carbachol produced hyperactivity which was attenuated by the coinfusion of isoproterenol. These results are consistent with the hypothesis that increases in diversive exploration and stimulus sampling induced by intrahippocampal norepinephrine are due to the activation of beta adrenergic receptors within the dentate gyrus.

Multivariate assessment of locomotor behavior: pharmacological and behavioral analyses.

A Behavioral Pattern Monitor (BPM) is described which is designed to assess the spatial and temporal sequences of the locomotor movements, investigatory holepokes, and rearings of rats. The system records these behavioral responses with 0.1 sec resolution in time and 1.5 inch resolution in space, and permanently stores all the resulting data. The sequences of these responses may then be displayed on a video terminal or on paper and are also available for the calculation of a variety of descriptive statistics. Studies are described in which rats were tested repeatedly without any pharmacological treatments or in single test sessions following the administration of saline or one of five stimulant drugs. A variety of descriptive measures of the temporal or spatial patterning of the animals' behavior are described and applied to the data resulting from the studies of the various stimulants. It is concluded that the combination of these measures enables distinctions to be made among these drugs which cannot be made on the basis of measures of the amount of locomotor activity.

Behavioral effects of xylamine-induced depletions of brain norepinephrine: interaction with amphetamine.

Male rats were treated with a combination of systemic fluoxetine and intraventricular xylamine in order to deplete brain norepinephrine (NE) in the projection areas of the locus coeruleus. Liquid chromatographic measures confirmed that xylamine reduced hippocampal NE by 77%. Four days later, control and lesioned rats were tested following subcutaneous injections of either saline or 1.0 mg/kg amphetamine in a Behavioral Pattern Monitor which recorded the sequential patterns of their locomotor and investigatory (holepokes) responses. Relative to controls, NE-depleted rats exhibited no alteration in the amount of spontaneous locomotor activity or its rate of habituation, but made fewer rearings and holepokes, particularly early in the hour test session. When challenged with 1.0 mg/kg amphetamine, sham-lesioned rats exhibited the expected increases in locomotor activity, holepokes, rearings, and both entries into and time spent in the center of the chamber. The lesioned animals exhibited a potentiation of the amphetamine effect on center activity and a diminished effect of amphetamine on holepoking and rearings. Control and lesioned rats were again tested at 18 days postlesion using the same test paradigm. The previously noted effects of the lesions on spontaneous behavior were absent at 18 days. Furthermore, the ability of these NE depletions to alter the behavioral effects of 1.0 mg/kg amphetamine at 4 days postlesion largely disappeared by 18 days. These results are indicative of some compensatory mechanism(s) operating to restore normal function between 4 and 18 days after the introduction of the lesion.