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Biomedical subjects

R T Bartus

Publications and source records attributed to R T Bartus.

At least 109 records · Page 6Linked to original sources
PubMed1979

Four stimulants of the central nervous system: effects on short-term memory in young versus aged monkeys.

Aged Rhesus monkeys and young control monkeys were tested in a delayed-response procedure to assess the effects of central-nervous-system (CNS) stimulants on short-term memory (STM). Previous research had established that the aged monkeys showed specific impairments of STM in this procedure. Four different CNS stimulants (methylphenidate, magnesium pemoline, a pentylenetetrazole/niacin mixture, and caffeine) were chosen for evaluation on the basis of their relevancy to current geriatric-psychopharmacologic research. Four different doses of each of the four CNS stimulants were given to each monkey, counter-balanced for possible order effects. Methylphenidate and caffeine impaired the performance of both age groups in this non-human primate cognitive task, even at relatively low dose levels. Magnesium pemoline produced fewer adverse effects and some evidence of improving STM in the aged monkeys, although not within the levels of statistical significance. The pentylenetetrazole/niacin mixture produced a three-way interaction involving age, dose and retention interval. This reflected the fact that although no definite effects were noted under the zero-sec control condition, statistically significant age-related deficits did occur in the STM-dependent retention interval as the dose varied. The data demonstrate that, of these four CNS stimulants, none radily improves (and often may impair) performance of tasks requiring STM. Thus the results of this study offer little support for the hypothesis that general CNS stimulation may constitute significant therapy for cognitive impairments associated with advanced age.

Aging↗
PubMed1978

Short-term memory in the rhesus monkey: effects of dopamine blockade via acute haloperidol administration.

The effects of dopaminergic blockade on recent or short-term memory (STM) were evaluated in test-sophisticated rhesus monkeys. Each monkey was tested under several doses of the antidopaminergic haloperidol (0.006 to 0.05 mg/kg), in an automated, delayed-response procedure. The same procedure and test apparatus had previously been used to demonstrate profound STM impairments in aged rhesus monkeys and strikingly similar deficits in young monkeys given the anticholinergic scopolamine. The results of this study do not support the notion that dopaminergic mechanisms play a critical role in primate STM. Although significant impairments in delayed-response accuracy were observed with the higher doses of haloperidol, this impairment was unrelated to the duration of the retention interval, implying a more general, non-mnemonic dysfunction. Since the qualitative nature of this deficit to dissimilar to, and not as specific as that previously found in aged rhesus monkeys (or young monkeys given scopolamine), it is suggested that age-related changes observed in the dopaminergic system are less likely to be responsible for the aged STM impairments than comparable age-related changes in the cholinergic system.

Animals↗
PubMed1978

Aging in the rhesus monkey: debilitating effects on short-term memory.

The performance of aged rhesus monkeys (18 years and older) was compared to that of young control monkeys (three to five years old) in three experiments designed to define and evaluate the presumed short-term memory impairment associated with aging. An automated, indirect delayed-response procedure was used with special emphasis directed toward controlling or eliminating potentially confounding variables such as attention, motivation, learning disabilities, etc. It was shown that the aged monkeys do suffer from a profound a specific impairment in short-term memory (STM), performing normally on the shortest dealy interval and showing progressively greater impairment as the retention interval was increased. A subsequent study varied deprivation level and demonstrated that it is unlikely that differences in motivation could account for the age-related STM deficits observed on the delayed-response task. Further studies indicated that alterations in stimulus availability did not differentially affect the performance of the two age groups to any measurable extent, suggesting that differences in stimulus processing abilities are neigher necessary nor sufficient conditions for the deficit found in the first experiment. These results suggest that the delayed-response deficity in old monkeys is directly related to age-associated changes in those areas of the nervous system which are important for the expression of short-term memory.

Aging↗
PubMed1977

Primate information processing under sodium pentobarbital and chlorpromazine: differential drug effects with tachistoscopically presented discriminative stimuli.

Sodium pentobarbital and chlorpromazine were evaluated for the degree to which they differentially reduce the speed or efficiency with which sensory information can be processed. Rhesus monkeys were tested under comparable doses of sodium pentobarbital and CPZ on a visual discrimination problem with varying durations of tachistoscopically presented stimulus information. When unlimited stimulus information was available, no effects of the two drugs were observed at the doses used, but as the duration of stimulus presentation was progressively decreased, the effects of sodium pentobarbital became more severe, whereas CPZ did not differe from the saline control an any presentation duration. While previously published literature indicates that CPZ impairs performance by intermittantly blocking sensory input or transmission, the present data provide the first direct behavioral confirmation that barbiturates impair performance by retarding the rate at which sensory stimuli can be processed and utilized.

Animals↗
PubMed1977

Frontal decortication in rhesus monkeys: a test of the interference hypothesis.

Four monkeys with dorsolateral frontal ablations and 3 unoperated controls were run on discrimination problems which sequentially presented both relevant and irrelevant visual stimuli prior to the opportunity for a choice response. As previously reported, monkeys with undamaged brains performed significantly better on those problems presenting relevant information first, being unaffected by later occurring irrelevant stimuli. Contrary to the behavior of the normal monkeys, monkeys with lesions of the dorsolateral frontal cortex were severely impaired when irrelevant stimuli were presented after the relevant stimuli had been processed, but before the opportunity to respond had occurred. In other words, the frontal monkeys performed just the opposite of the normals in these procedures, even though the relevant and irrelevant stimuli were manipulated within the usual temporal definitions of the two-choice discrimination trial. These data demonstrate that the presentation of irrelevant stimuli before the choice response can significantly impair frontally decorticated monkeys and that this impairment does not require the use of a long temporal delay preceding the opportunity to respond. For this reason the data were interpreted as rather direct support of the interference hypothesis of frontal dysfunction. On the basis of these and other data discussed, it was concluded that one function of the dorsolated frontal cortex involves the suppression of interfering stimulus events interposed between the information necessary to guide behavior and the behavior itself.

Animals↗
PubMed1976

Short-term memory in the rhesus monkey: disruption from the anti-cholinergic scopolamine.

Two separate experiments were conducted to evaluate the effects of the anti-cholinergic scopolamine on primate visual discrimination and short-term memory (STM). In the first experiment it was shown that relatively mild doses of scopolamine severly impaired visual discrimination performance, even though the test procedure provided strong stimulus control. This deficit in visual discrimination suggested that previous research which used the delayed matching to sample procedure (DMS) to evaluate the role of cholinergics in primate STM may have confounded an accurate measure of specific STM effects because the DMS is inherently dependent on accurate visual discrimination. Therefore, the second experiment evaluated the effects of scopolamine on STM, using an automated apparatus and test procedure designed to minimize the discrimination component and other confounding variables present in the earlier research. In this second experiment, an indirect delayed response (DR) procedure was used, measuring the monkeys' ability to recall simple stimulus events over retention intervals of 0, 2.5, 5, and 10 sec. The monkeys were tested under 2 doses of the anti-cholinergic scopolamine and their performance was compared to that obtained on several nondrug control days. Contrary to earlier reports using the DMS, a clear interaction of drug and retention interval occurred in this situation. Under scopolamine, greatest impairments occurred on the longest delays, with little or no effect with zero second retention. Furthermore, the impairments observed on the longer delays were even greater with the highest dose of scopolamine. These data, therefore,support the notion that cholinergic mechanisms play an important role in the expression of STM in primates.

Acetylcholine↗
PubMed1975

Effect of nitrogen narcosis on cortical and subcortical evoked responses in the cat.

Four cats were chronically implanted with gross, monopolar electrodes in the lateral geniculate nucleus (LGN), pretectum-superior colliculus (P-SC), primary visual cortex (VI), and secondary visual cortex (VII). Following recovery and preliminary testing, the animals were dived in a dry hyperbaric chamber to the sea water equivalent of 103 m (i.e. 340 ft.) where visual evoked responses were recorded. No decrements in the amplitude of the visual evoked response were found at the LGN, but significant decreases did occur at the other three sites. These data suggested: 1) that the effects of nitrogen narcosis on the visual system are primarily central, and not simply peripheral in nature; 2) that these effects are not limited to the visual cortical mantle; and 3) that the narcosis apparently influences structures involving different anatomical levels of the brain which presumably mediate various types of visual processes. The findings were discussed as they relate to current ideas concerning the underlying neurological causes and behavioral effects of nitrogen narcosis.

Animals↗