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The higher level cognitive function of planning was studied in a group of medicated Parkinson's disease patients and a group of matched control subjects, using a computerised version of Shallice's Tower of London task. Baseline measurement of the ability to execute a given plan of action, to generate low level strategies required for efficient searching, and spatial working memory capacity, all of which contribute to performance on the planning task, established that the Parkinson's disease group was unimpaired on any of these measures. On the Tower of London task, the Parkinson's disease group was also unimpaired in terms of the average number of moves required to solve a problem. However, a specific planning deficit was evident when "thinking" times were analysed, and this was after the confounding influence of motor initiation and execution times had been carefully extracted from total performance times. This finding is discussed in relation to putative functions of the frontal lobes and basal ganglia, and an attention-switching hypothesis is developed to account for it.

Groups of patients with dementia of Alzheimer type (DAT) and idiopathic Parkinson's disease, together with age and IQ-matched normal controls, were compared on several computerized tests of visuospatial memory and learning. Two different groups of parkinsonian patients were studied: (1) a newly diagnosed group, early in the course of the disease, not receiving medication (NMED) PD) and (2) a group later in the course of the disease, receiving medication (MED PD). The DAT and MED PD group were significantly impaired in both spatial and visual pattern recognition memory. The DAT group exhibited a delay-dependent deficit (over 0-16 s) in a delayed matching-to-sample procedure, but were not impaired at simultaneous-matching-to-sample. By contrast, the MED PD group showed delay-independent deficits in the delayed matching-to-sample test and both the MED PD and the NMED PD group were also significantly impaired in simultaneous matching. In a form of delayed response test, the subjects were required first to memorize and then to learn the locations of several abstract visual stimuli which varied progressively in number from 1 to 8. The DAT group were severely impaired in this conditional associative learning task. A significant proportion of patients, but none of the controls, in the NMED and MED PD group also failed the test at the levels of 6 or 8 items. There was a significant correlation between the performance on the first trial, memory score in the delayed response task and indices of clinical disability and disease duration in the patients with Parkinson's disease. The results are discussed in terms of the utility of the comparison between DAT and PD in characterizing the nature of the cognitive deficits in these conditions and their relation to those findings from animal neuropsychology which use comparable paradigms.

Rats were reared in social isolation or in social groups of 4 or 5 rats per cage from weaning and were fed either a lab chow diet or a diet of 4 palatable foods (cafeteria diet), in addition to the lab chow. The hyperactivity of isolation-reared rats appears to be a reactivity to novel environmental stimuli, since it was seen only in the 0.5 hr tests and not in the near 24 hr test. It was found that hyperactivity and increased body weight can develop within as few as 7 to 10 days in rats reared in isolation from weaning. Cafeteria feeding enhanced activity in isolation-reared rats, but suppressed it in group-reared rats. Isolation-reared rats fed a cafeteria diet had strong, stable preferences for their most preferred food over the 25 days of measurement. Rats reared in isolation had significantly different food preferences, as compared with rats reared in groups. Cafeteria fed rats had a significantly greater calorie intake and body weight than rats fed lab chow. On analysis, cafeteria fed rats had significantly greater carcass energy and an increased amount of parametrial white adipose tissue as compared with rats fed only lab chow. The interscapular brown adipose tissue (IBAT) weights of cafeteria fed rats were also greater. However, as there was no difference between the cafeteria and chow fed rats in the total amount of protein in the IBAT, it was concluded that the increased weight of the IBAT did not reflect a genuine hypertrophy of the tissue.

3,4-Dihydroxyphenylethylamine (DA, dopamine) and 5-hydroxytryptamine (5-HT) turnover values were determined in freely moving male rats by measuring the rates of accumulation of the acidic metabolites of the above transmitters, i.e., 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (CSF) samples after probenecid (200 mg/kg i.p.) administration. Determinations on samples before and after acid hydrolysis showed that the latter procedure was necessary for DA turnover determination. Thus whereas total (DOPAC + HVA) increased linearly with time after probenecid, free (DOPAC + HVA) did not. This was because the percentage of DOPAC + HVA in conjugated form increased with time. Determinations on a group of 28 rats during the dark (red light) period showed that cisternal amine metabolite concentrations before probenecid injection did not parallel turnover values. This was probably because individual differences in metabolite egress strongly affect the pre-probenecid values. The poor correlations between CSF tryptophan and 5-HT turnover suggested that differences of brain tryptophan concentration were not major determinants of differences of brain 5-HT metabolism within this group of normal rats. Considering that the rats were of similar weight and that the turnover values were all determined at approximately the same time of day, the three- to fourfold ranges of the turnover values are remarkable. The positive correlation between the DA and 5-HT turnovers of individual rats suggests the existence of common effects on DA and 5-HT turnover in normal rats.

The effects of 5, 10, and 20 mg/kg chlordiazepoxide on tail pinch (TP)-induced behavior were investigated. Five mg/kg enhanced TP-induced eating in terms of both latency and duration. Twenty mg/kg had decremental effects. All doses of the drug reduced the incidence of clip-directed behavior, but increased locomotor activity during the TP trials in a dose-dependent manner. On control trials, the drug increased locomotor activity at the low dose and eating at the high dose. The results are examined in terms of the various behavioral actions of the minor tranquilizers. The implications for the behavioral and neuropharmacological mechanisms underlying TP-induced and other forms of stimulus-bound behavior are discussed.

The effects of physostigmine on test performance of a patient with multiple cognitive deficits were observed in a double-blind, placebo-controlled study. Scores on tests of learning and memory and tests of visuo-spatial and constructional ability were both improved by physostigmine, while lecithin improved scores only on the former tests.

Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.

Seventeen male Sprague-Dawley rats were trained to eight to nine correct responses on a delayed spatial alternation test performed on alternate days in a T-maze. Locomotor activity in an observation box was scored on 2 consecutive days. The animals were killed 2 weeks after the end of behavioural testing and dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5HT), the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the 5HT metabolite 5-hydroxyindoleacetic acid (5HIAA) determined in cortex, hippocampus, striatum and hypothalamus. Cortical concentrations of both DA and NA correlated negatively and significantly with the number of errors made in learning the alternation task, though the latter correlation was less striking and became negligible after the correlation between DA and NA was partialled out. Concentrations of DA and NA in the other regions did not correlate significantly with errors. None of the other neurochemical variables correlated significantly with either errors or locomotor activity, except for hypothalamic HVA concentration which showed a marginally significant correlation with locomotor activity. The above results, together with effects of brain lesions reported by other authors, strongly indicate that cortical catecholamines facilitate learning in the normal non-drug-treated rat.