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Biomedical subjects

R W Pelham

Publications and source records attributed to R W Pelham.

13 recordsLinked to original sources
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↗
PubMed1980

Prolonged ethanol consumption produces persistent alterations of cholinergic function in rat brain.

Prolonged ethanol consumption produces neuropathology and neurologic symptoms in humans and experimental animals. As a means of understanding the central nervous system (CNS) consequences of ethanol abuse, we sought whether cholinergic neurochemical functions were altered by long-term ethanol consumption by rats. Eighteen weeks of ethanol consumption in a liquid diet reduced rat striatal and mammillary body choline acetylase (ChAT) by 53% and 58%, respectively. In these same regions, the density of muscarinic cholinergic receptors was elevated 117% and 12%. No such alterations were observed in cortex or in hippocampus. No alterations followed short-term ethanol consumption (2 wk), but they persisted after ethanol withdrawal (4 wk). After 13 mo of ethanol consumption, the number of neuroleptic binding sites in striatum was diminished by 29%. These results demonstrate a persistent, possibly permanent, alteration in brain cholinergic function as a consequence of long-term ethanol ingestion. Since brain acetylcholine is involved in numerous neurologic functions, including memory processes, these findings may be relevant to the lasting memory disorder and other permanent effects associated with chronic alcoholism.

Alcoholism↗
PubMed1979

Identification of direct competition for, and indirect influences on, striatal muscarinic cholinergic receptors: in vivo [3H]quinuclidinyl benzilate binding in rats.

[3H]Quinuclidinyl benzilate (QNB) binds to specific muscarinic receptors of rat striatum, in vivo. The binding is saturable and displaceable by muscarinic drugs. Clozapine and thioridazine are unique antipsychotic agents with low liability for extrapyramidal side-effects, and both displaced ONB, while several other neuroleptics did not. In addition to this apparent direct competition for cholinergic receptors, morphine and amphetamine increased ONB binding by indirect influences on muscarinic receptors. In vivo QNB binding not only confirms in vitro findings, but it also detects indirect, probably transsynaptic, alterations of muscarinic cholinergic receptor dynamics.

Animals↗
PubMed1979

Endocrine factors contributing to the ethanol preferences of rodents.

Groups of C57 Bl/6j mice (alcohol preferring) and DBA/2j mice (alcohol avoiding) were fasted for 24 hours and administered glucose. At 30, 120 and 300 minutes after glucose, the C57 Bl/6j mice had significantly higher levels of plasma glucose than the DBA/2j strain. These differences were observed in comparable groups given either forced access or no access to alcohol. In ad lib fed animals never exposed to alcohol, C57 Bl/6j mice had higher levels of plasma insulin than DBA/2j mice. Plasma levels of glucose and corticosterone were not significantly different in ad lib or fasted animals. The injection of insulin zinc protamine to DBA/2j mice produced 100% convulsions within one hour, but produced to convulsions in C57 Bl/6j mice for as long as 4 hours after administration. These data demonstrate that an insulin resistancy exists in C57 Bl/6j mice which is not dependent upon any prior alcohol experience. Evidence supporting a functional relationship between this diabetogenic disturbance and alcohol preference was obtained in C57 Bl/6j mice which were allowed to choose between water or a 10% alcohol solution (v/v). Insulin zinc protamine produced a selective dose-dependent reduction in alcohol intake. Additional support is received from the discovery that Chinese hamsters, a species genetically predisposed to diabetes, display an impressive preference for 10% alcohol.

Alcohol Drinking↗
PubMed1979

A rat model (using a semipurified diet) of the fetal alcohol syndrome.

A semipurified liquid diet was used to develop a chronic rat model of the fetal alcohol syndrome. Control female rats gained weight normally, reproduced normally, and gave birth to normal litters on this diet. Increased neonatal mortality, decreased neonatal weights, and altered sex ratios were observed in offspring of experimental alcoholic animals. Preliminary histological results include a mild delay in cell lamination patterns in the cerebral cortex at 4 days postnatal in alcoholic offspring as well as decreased formation of dendritic spines at 7 days postnatal.

Animals↗
PubMed1976

Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs.

In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects.

Adult↗
PubMed1975

A serum melatonin rhythm in chickens and its abolition by pinealectomy.

Melatonin, a suspected hormone of the pineal organ, was extracted from chicken serum and quantified by the Rana pipiens bioassay. When chickens were housed in an alternating light-dark photoperiod, serum melatonin was usually not detected during the light phase. Serum melatonin rose within 1 hr after the lights were extinguished, plateaued around midnight and fell before the lights were turned on. Serum melatonin was not detected at any time of day in pinealectomized chickens, suggesting that the pineal is neccessary for, and may be the source of, circulating melatonin.

Animals↗
PubMedDate not supplied

Animal models of alcoholic neuropathy: morphologic, electrophysiologic, and biochemical findings.

A chronic high alcohol intake was induced in rats through the use of two procedures: the schedule-induced polydipsia technique and the liquid diet technique. Rats consumed 11-12 g of ethanol per kilogram body weight per day for 16 to 18 weeks. Morphologic evidence of a mild distal axonal neuropathy in the ventral caudal nerve was proposed. The red blood cell transketolase levels were normal, indicating that the rats were not deficient in thiamine and suggesting that the axonal degeneration was due to the direct toxic effect of alcohol. Axonal transport studies demonstrated a significant increase in the amount of acetylcholinesterase transported in an orthograde direction in the sciatic nerves of alcohol-exposed rats, and indicated no change in the transport of choline acetyltransferase or in the specific binding of colchicine by neurotubulin.

Acetylcholinesterase↗