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Biomedical subjects

J E Morley

Publications and source records attributed to J E Morley.

At least 19 recordsLinked to original sources
PubMed1992

Effect on memory processing by D-cycloserine, an agonist of the NMDA/glycine receptor.

Glycine has been shown to modulate N-methyl-D-aspartate (NMDA) subclass of acidic amino acid receptors which have been implicated in learning and memory. We report that d-cycloserine (DCS) which has a high affinity for the glycine modulatory site in the NMDA receptor complex modulated memory processing in a dose-dependent manner. Mice were trained on a footshock avoidance task. Immediately after training DCS was administered (2.5 to 50 mg/kg s.c.). When retention was tested a week later, 20 mg/kg facilitated retention the best with lower and higher doses be less effective in weakly trained young mice. DCS also facilitated retention in 'senescence-accelerated mice' in which impairment of learning and memory increases with age. DCS had to be administered at higher doses to improve retention as impairment of learning and memory increased.

Age Factors↗
PubMed1992

Evidence that cholecystokinin-enhanced retention is mediated by changes in opioid activity in the amygdala.

Mice, partially trained to avoid footshock in a T-maze, showed enhanced retention relative to vehicle-injected mice when treated peripherally with arecoline, D-amphetamine, cholecystokinin octapeptide (CCK-8), epinephrine or naloxone. Both intra-amygdaloid and intraventricular injections of beta-endorphin resulted in amnesia. D-amphetamine and arecoline blocked the amnestic effect of beta-endorphin administered into the amygdala but it required higher doses for CCK-8, epinephrine and naloxone to block the amnestic effect of beta-endorphin. The effects of CCK-8, epinephrine and naloxone showed a differential ability to block amnesia induced by beta-endorphin intraventricularly with epinephrine and naloxone preventing amnesia but CCK-8 not improving retention. This data suggests that the memory enhancement produced by peripherally administered CCK-8 involves the amygdala and that both CCK-8 and epinephrine interact with opioid amnestic mechanisms within the amygdala to alter memory processing.

Amygdala↗
PubMed1992

Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it.

Immediate post-training intracerebroventricular administration to male mice of pregnenolone (P), pregnenolone sulfate (PS), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, dihydrotestosterone, or aldosterone caused improvement of retention for footshock active avoidance training, while estrone, estradiol, progesterone, or 16 beta-bromoepiandrosterone did not. Dose-response curves were obtained for P, PS, DHEA, and testosterone. P and PS were the most potent, PS showing significant effects at 3.5 fmol per mouse. The active steroids did not show discernible structural features or known membrane or biochemical effects that correlated with their memory-enhancing capacity. The above, together with the findings that DHEA acted even when given at 1 hr after training and that P, PS, and DHEA improved retention over a much wider dose range than do excitatory memory enhancers, led to the suggestion that the effects of the active steroids converge at the facilitation of transcription of immediate-early genes. P and PS, for which receptors have not yet been demonstrated, may exert their effects by serving as precursors for the formation of a panoply of different steroids, ensuring near-optimal modulation of transcription of immediate-early genes required for achieving the plastic changes of memory processes. Low serum levels of P in aging and the increases of cancer and behavioral disorders in individuals receiving drugs that block synthesis of cholesterol, the immediate precursor of P, suggest possible clinical utility for P.

Animals↗
PubMed1992

Age-related changes in LFA-1 expression, cell adhesion, and PHA-induced proliferation by lymphocytes from senescence-accelerated mouse (SAM)-P/8 and SAM-R/1 substrains.

Accelerated senescence-prone mice of the SAM-P/8jf series were compared with senescence-resistant SAM-R/1 controls in terms of age-related changes in phytohemagglutinin (PHA) proliferative responses and lymphocyte function-associated antigen-1 (LFA-1) utilization by non-adherent splenocytes. Advancing age was associated with a reduction in cell proliferative responses to PHA in both substrains, although the rate of decline was significantly more rapid in the senescence-prone animals. Conversely, in both substrains there was a progressive age-related increase in the proportion of splenocytes expressing high levels of LFA-1, and a parallel increase in the degree of LFA-1-dependent cell aggregation induced by phorbol ester. Age-matched SAM-P/8jf and SAM-R/1 mice did not differ in terms of LFA-1 expression or LFA-1-dependent cell aggregation. Two-color cytofluorometric analysis demonstrated the enhanced expression of LFA-1 expression by cells bearing the Pgp-1hi phenotype characteristic of memory lymphocytes. These results suggest that age-associated changes in lymphocyte adhesion are attributable to alterations in the relative numbers of memory cells expressing high levels of LFA-1, but are unlikely to contribute to the reduced proliferative response to mitogen in aged mice.

Aging↗
PubMed1992

Competitive antagonism of nitric oxide synthetase causes weight loss in mice.

These studies demonstrate that the competitive antagonist of nitric oxide synthesis, L-NG-nitro-arginine methyl ester (NO Arg ME), produces an L-arginine reversible decrease in food intake in mice. NO Arg ME also blocked the feeding effect of the potent orexigenic peptide, neuropeptide Y. NO Arg ME produced weight loss when administered over 5 days. The studies suggest that nitric oxide is a physiological modulator of food intake and that nitric oxide synthetase inhibitors may be useful in the management of obesity.

Amino Acid Oxidoreductases↗
PubMed1992

Amylin.

Amylin is a 37 amino-acid peptide which is secreted from the pancreatic islets of Langerhans. It has major sequence homology with calcitonin gene related peptide. Amylin can precipitate out in these cells to form amyloid. Amylin is secreted by similar stimuli to those that secrete insulin. Amylin has a number of effects that may counteract the effect of secreted insulin, i.e., decreased second phase insulin secretion, increased hepatic glucose output, and inhibition of insulin effects on skeletal muscle. It must, however, be recognized that in many cases the doses necessary to produce these effects appear to be supraphysiological. The putative role of amylin in the hyperglycemia of aging and Type II diabetes mellitus therefore remains controversial. Amylin has a number of other effects including inhibition of osteoclastic activity, vasodilatation, anorectic effects and enhanced memory retention. This review postulates a role for amylin in the pathogenesis of a number of age-related changes.

Aging↗
PubMed1992

Effects of peripheral hormones on memory and ingestive behaviors.

This article explores the mechanisms by which peripheral gastrointestinal hormones produce central nervous system effects on memory and feeding. Cholecystokinin produces its satiety effects and memory-enhancing effects by stimulating ascending vagal fibers. Hyperglycemia has been demonstrated to be a cause of memory dysfunction in persons with diabetes mellitus. A number of other hormones, such as amylin and bombesin, modulate both memory processing and feeding. The causes of the anorexia of aging are briefly reviewed.

Aging↗
PubMed1992

Early onset of age-related impairment of aversive and appetitive learning in the SAM-P/8 mouse.

SAM-P/8 (P/8if) mice, trained on aversive and appetitive training tasks, showed age-related impairment of learning on more difficult tasks. Using aversive training tasks, acquisition of step-down passive avoidance did not differ between 4- and 12-month-old mice. T-maze footshock avoidance acquisition detected impairment from 9 to 12 months of age. On the appetitive tasks, 12-month-old mice required significantly more trails than 4-month-old mice to learn to press a lever for milk reinforcement or to learn a specific sequence of 10 black-white, left-right discriminations. However, learning a simple black-white discrimination in the same 10-unit maze did not discriminate between the performance of 4- and 12-month-old mice. A lack of age-related changes in food, water, and milk consumption suggests that changes in motivation do not account for the decline in learning in older P/8if mice. The results suggest an early onset of impaired learning relative to the 17.2-month median life span of the P/8if mice.

Aging↗
PubMed1992

Role of the opioid system in the hypodipsia associated with aging.

OBJECTIVE: To compare the effects of the opioid antagonist, naloxone, on fluid ingestion in young and older males, in order to estimate the role of the opioid system in hypodipsia of older men. DESIGN: Single-blinded, randomized, cross-over, placebo-controlled study. SETTING: Outpatient Department of Veterans Affairs. STUDY PARTICIPANTS: Sixteen young subjects (aged 23 to 39) and eight older subjects (aged 69 to 75). All subjects were healthy, community-dwelling, non-smoking men, on no medications. INTERVENTION: Subjects were randomized to receive either placebo or naloxone on day one. Whichever substance the subject did not receive was given on day two with days one and two separated by at least a 2-week washout period. MAIN OUTCOME MEASURES: Fluid intake after overnight food and fluid deprivation, with placebo or naloxone injected in the morning. RESULTS: After overnight fluid deprivation, older individuals consumed 29% less fluid in 2 hours compared with younger individuals (ns). After overnight fluid deprivation and injection with naloxone 100 micrograms/kg, fluid intake was diminished by 42% (P less than 0.05) in young subjects compared with placebo, but only by 7% (ns) in older subjects. Subjective ratings did not differ significantly between young and old subjects. CONCLUSIONS: These preliminary data suggest that the opioid system plays a role in the drinking response in young subjects while failing to alter fluid intake in older subjects. Hypodipsia in older individuals may be due to a deficit in the opioid drinking drive.

Adult↗
PubMed1991

Evidence that nitric oxide modulates food intake in mice.

Nitric oxide (NO) may be an intercellular modulator within the central nervous system. L-arginine, which results in NO synthesis, increased food intake in mice while the inhibitor of NO synthesis, L-NG-nitro arginine (L-NO Arg) inhibited food intake in food deprived mice. L-arginine, but not D-arginine, partially reversed the inhibitory effect of L-NO Arg on food intake. These findings suggest the possibility that NO may be a physiological modulator of food intake and that the possibility of exploring the utility of L-NO arg in the treatment of obesity should be explored.

Animals↗
PubMed1991

Opinions about management of geriatric syndromes given by internal medicine residents in two programs.

Internal medicine residents in two programs providing different amounts of training in geriatrics were surveyed in 1988 regarding their opinions about the management of four geriatric problems and two traditional internal medicine problems. The residents generally agreed that geriatric problems were legitimate concerns in a general internal medicine practice but demonstrated less confidence in the management of geriatric problems than in the management of traditional problems. Residents from the program that provided more extensive training in geriatrics evidenced greater support for nondiscriminatory care of elderly diabetics; otherwise there was no convincing evidence of differences between the two programs. The authors conclude that educational efforts in geriatrics need to target trainees' confidence in the management of geriatric problems.

California↗
PubMed1991

mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.

Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.

Animals↗