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Biomedical subjects

R L Dean

Publications and source records attributed to R L Dean.

51 records · Page 3Linked to original sources
PubMed1981

Presynaptic cholinergic mechanisms in brain of aged rats with memory impairments.

Presynaptic cholinergic mechanisms were investigated in various brain regions of aged Fisher 344 rats with documented 24 hr retention deficits measured in a single-trial passive avoidance tasks. Sodium-dependent high affinity choline uptake was found to be decreased by 22% in hippocampus of 23-26 month old animals as compared to 6 month old controls. Prior depolarization of hippocampal or cortical synaptosomes with K+ resulted in stimulation of choline uptake which was similar in aged rats and young controls. No age-related differences were observed either in hippocampal, cortical, striatal acetylcholine or choline concentrations, or in the activity of choline acetyltransferase in hippocampus. Synthesis of acetylcholine in hippocampal and cortical slices under basal conditions, as well as under K+-stimulated concentrations, did not differ in the two age groups examined. These neurochemical findings are consistent with an age-related decrease in hippocampal cholinergic neuronal activity without an actual loss in cholinergic neuron number. It is further suggested that this reduction in cholinergic neuronal activity may be related to the deficit in cognitive performance observed in aged Fisher rats.

Acetylcholine↗
PubMed1981

Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats.

In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances, aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a one trial passive avoidance task, and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (p less than 0.05), but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. In a second study, it was shown that twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6-10%). No significant changes following choline administration were observed in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data are discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one parameter of a deficient metabolic pathway.

Acetylcholine↗
PubMed1981

Age-related differences in behavior across the life span of the C57BL/6J mouse.

C57Bl/6J mice, representing four divergent age groups (ranging from 3 months to 31 months) were each tested on a number of behavioral procedures, selected to sample a wide spectrum of behaviors. The evaluation demonstrated that, as with other mammalian species, not all behaviors in the mouse are affected by old age. Most severely impaired was retention of a single-trial passive avoidance task, most probably reflecting a deficit in memory ability. One tests of motor function, the most demanding tasks revealed the greatest debilitating effects of age, paralleling the effects of task difficulty previously reported in numerous learning studies. Finally, a deficit in the ability to modify preexisting habits in a T-maze learning situation was observed, corroborating reports of increased perseveration in aged humans and nonhuman primates. The similarity of these results across the life span of the C57 mouse with those previously reported for other aged mammalian species demonstrates that certain common types of behaviors seem to be impaired selectively by increased age across mammalian species and raises the possibility that common neurological etiologies may exist for these behavioral deficits.

Aging↗
PubMed1980

Brain cholinergic dysfunction and memory in aged rats.

Age related alterations in mnemonic ability and in the functional status of muscarinic receptors were evaluated and compared to biochemical measures of pre and post-synaptic cholinergic functioning. Retention of a single trial passive avoidance task was considerably disturbed as a function of aging. The functional status of muscarinic receptors, as measured by the ability of microiontophoretically applied acetylcholine to stimulate the firing of hippocampal pyramidal cells, was similarly disturbed in aged rats. A small, but significant decrease in muscarinic receptors was detected in the dorsal hippocampi of these same aged rats, while choline acetyltransferase activity did not change. When considered with prior psychopharmacological studies, these data suggest that specific muscarinic receptor impairments may play a critical role in the memory disturbances associated with old age.

Acetylcholine↗
PubMed1979

Recent memory in aged non-human primates: hypersensitivity to visual interference during retention.

The effect of irrelevant visual information presented during retention of recent memory was investigated in young and aged monkeys. The monkeys were required to remember the location of a visual stimulus over short durations, during which time, on certain trials, irrelevant visual stimulation was presented. It was found that although the young monkeys performed as well with or without the irrelevant stimulation, the aged monkeys were significantly impaired when irrelevant stimulation was presented. Thus, these data provide direct support for the notions that aged subjects suffer a decreased ability to suppress visual stimuli from interfering with accurate behavior, and that this disability contributes to the memory impairments reported with old age. When considered with previous research in humans and non-human primates, these results suggest that this disability to suppress sensory interference may reflect a general effect of aging which may contribute to many other age-related behavioral impairments. Finally, it was suggested that the striking similarities of the behavioral profile now established for the aged monkey to that of younger monkeys suffering destruction of the frontal cortex (and anatomically related subcortical sites) offers the heuristic possibility that these two syndromes share a common neurological etiology.

Aging↗
PubMed1979

Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning.

The behavior of aged rhesus monkeys (18 years and older) was compared to that of young monkeys (3 to 6 years old) to evaluate their relative abilities to learn a series of visual discrimination and discrimination reversal problems. Using a subject-paced, automated experimental procedure designed to optimize stimulus control and facilitate execution of choice responses, no consistent age-related differences were observed in the ability to learn new color and pattern discrimination problems of varying difficulty. However, a severe and consistent deficity on reversal learning did occur. A detailed analysis of this deficit revealed that not only did the aged monkeys take longer to extinguish the old habit and return to chance performance, but they continued to display a deficit in establishing accurate performance at above-chance levels as well. Since no reliable age differences were observed on the original discrimination learning problems, these data suggest that aging impairs mechanisms involved with response rigidity and/or susceptibility to intertrial proactive interference, more severely than those involved with the simple formation of new associations.

Aging↗
PubMedDate not supplied

Tetrahydroaminoacridine, 3,4 diaminopyridine and physostigmine: direct comparison of effects on memory in aged primates.

The effects of tetrahydroaminoacridine (THA), 3,4 diaminopyridine (3,4 DAP) and physostigmine were evaluated for their ability to reduce memory impairments in aged, test-sophisticated cebus monkeys (18 to 26 years old). Several doses of each drug were tested (PO) in each of ten different monkeys, allowing for direct and extensive comparison of each drug's efficacy in this model. The results of this comparative test revealed several potentially interesting findings: (1) all drugs produced improvement in a portion of the monkeys tested; (2) as in many past tests with aged monkeys and humans, wide variations in most effective dose, per subject, were observed; (3) different monkeys responded more effectively to one drug than another; and (4) under these tightly controlled conditions, physostigmine produced the most reliable and robust effects (p less than 0.005), in more monkeys, than did either THA (p less than 0.05) or 3,4 DAP (p less than 0.10).

4-Aminopyridine↗
PubMedDate not supplied

Lack of efficacy of clonidine on memory in aged cebus monkeys.

Using a dosing paradigm and an automated behavioral testing procedure designed to maximize potential drug efficacy, we evaluated the ability of clonidine to improve performance of aged monkeys on a trial-specific memory task. These results indicated that neither acutely administered (0.0025-0.04 mg/kg) or subchronically administered (0.01-0.06 mg/kg for 3 consecutive days) clonidine improved the performance of aged monkeys. These data are discussed in view of previously reported, conflicting data, as well as their implication regarding probable neurochemical factors involved in age-associated memory impairment and approaches to future palliative treatments.

Aging↗