Biomedical subjects

P E Gold

Publications and source records attributed to P E Gold.

At least 19 recordsLinked to original sources

PubMed1992

Spontaneous alternation and inhibitory avoidance impairments with morphine injections into the medial septum. Attenuation by glucose administration.

Peripheral glucose administration attenuates impairments produced by peripheral injections of the opioid agonist, morphine, on spontaneous alternation. Injections of opioid agonists directly into the medial septum also impair memory. The present experiments examined whether systemic and intraseptal glucose injections could attenuate deficits on spontaneous alternation and inhibitory avoidance in rats treated with intraseptal morphine. Morphine (3.95 nmol) injected into the medial septum significantly impaired performance on spontaneous alternation and inhibitory avoidance tasks. Both systemic (100 mg/kg, i.p.) and intraseptal (18.33 nmol) injections of glucose, administered concomitantly with intraseptal morphine, attenuated the morphine-induced impairments on these tasks in rats. These findings suggest that one brain region where glucose may act is the medial septum, possibly by releasing opioid inhibition of cholinergic activity.

Animals↗

PubMed1992

Plasma glucose levels predict the disrupting effects of adrenoceptor antagonists on enhancement of memory storage.

Adrenoceptor antagonists block the enhancement of memory storage produced by epinephrine injection, but not that produced by glucose injection. The present experiment determined whether adrenoceptor antagonists modify resting blood glucose levels or the magnitude of epinephrine-, glucose-, and footshock-induced increases in circulating glucose levels in a manner related to these previously observed effects on memory. The alpha- and beta-adrenoceptor antagonists, phenoxybenzamine and propranolol, respectively, were injected in rats 30 min prior to administration of epinephrine, glucose, or footshock. Plasma glucose levels were sampled during the next 30 min. Epinephrine-induced increases in plasma glucose levels were potentiated by phenoxybenzamine and were attenuated and delayed by propranolol. The adrenoceptor antagonists did not alter resting plasma glucose levels, or the increases in plasma glucose levels resulting from glucose injection or footshock. These findings suggest that phenoxybenzamine and propranolol alter blood glucose responses to epinephrine injection in a manner which may contribute to attenuation of epinephrine-induced enhancement of memory storage with peripheral injections of adrenoceptor antagonists.

Animals↗

PubMed1992

Enhancement of REM sleep with auditory stimulation in young and old rats.

Auditory stimulation applied during rapid eye movement (REM) sleep enhances the duration of REM sleep in cats and humans. The present experiment investigated whether auditory stimulation would enhance REM sleep in young (3-6 months) rats, and also in old (22-24 months) rats which have impaired REM sleep. Baseline sleep records were obtained on two days. Sleep patterns were then assessed during auditory stimulation test sessions. In young rats, auditory stimulation was administered during each REM sleep bout. In old rats, auditory stimulation was administered on a fixed schedule (10 min of stimulation alternating with 15 min quiet). The day after the stimulation session, an additional sleep record (Day 2) was obtained for each rat. In young rats, auditory stimulation enhanced both REM sleep duration and total REM sleep time. In the old rats, which showed impaired sleep measures as compared to young animals, auditory stimulation enhanced both total REM sleep time and the number of REM sleep periods. Residual proactive effects of auditory stimulation (Day 2) were observed in both young and old rats. Thus, auditory stimulation is an effective manipulation with which to augment REM sleep in both young and old rats, and partially attenuates REM sleep impairments in old rats.

Acoustic Stimulation↗

PubMed1992

Sleep deficits in rats after NMDA receptor blockade.

N-Methyl-D-aspartate (NMDA) receptor blockade disrupts a variety of functions associated with neural plasticity, including acquisition of learned responses and long-term potentiation. Deficits in memory are significantly correlated with deficits in measures of paradoxical sleep in several amnesic populations. The present experiment therefore assessed whether NPC 12626, a competitive NMDA receptor antagonist, also disrupts sleep. NPC 12626 (1, 10, 50, and 100 mg/kg) or saline was administered to Sprague-Dawley rats 30 min prior to 3-h daytime recording periods. Paradoxical sleep was selectively impaired at all but the highest dose, which prevented all sleep during the recording period. Some deficits in nonparadoxical sleep first appeared at the 10 mg/kg dose but did not became prominent until the 50 mg/kg dose. The results thus show that NPC 12626 impairs sleep states in rats and demonstrate that paradoxical sleep is particularly susceptible to the effects of NMDA receptor blockade. These findings, along with previous evidence that NMDA antagonists impair waking measures of arousal, provide evidence that all sleep-wake states are impaired by NMDA receptor blockade. More generally, the results suggest that some brain mechanisms underlying sleep and memory may share common elements.

Amino Acids↗

PubMed1992

Phlorizin enhancement of memory in rats and mice.

Glucose administration near the time of training or testing elevates blood glucose levels and enhances memory in rodents and humans. The magnitude of increases in circulating glucose levels predicts later retention performance in these and several other situations. Thus, circulating glucose levels appear to contribute to the regulation of memory storage processes. Phlorizin is an inhibitor of glucose transport, which, in view of the effects of glucose on memory, should impair memory. However, rats and mice injected with phlorizin before training in an inhibitory (passive) avoidance task demonstrated significantly enhanced memory performance compared to that of control animals. The effective dose of phlorizin did not significantly change regional brain-relative 3H-2-deoxyglucose uptake or plasma glucose levels. To summarize, phlorizin is a potent memory-enhancing drug. While the mechanism of this enhancement is unknown, it does not appear to include changes in blood glucose levels or brain glucose uptake.

Animals↗

PubMed1992

Anterograde and retrograde enhancement of 24-h memory by glucose in elderly humans.

The present experiment examined anterograde and retrograde enhancement of memory storage by glucose in elderly humans. Glucose (50 g) or saccharin was administered shortly before or immediately after acquisition of a narrative prose passage. Recall was tested 24 h later. Glucose administration before or after presentation of the material to be learned significantly improved recall 24 h later compared to performance in the saccharin condition. These findings suggest that glucose retroactively enhances memory storage processing in elderly humans and that the enhancement of memory outlasts the transient elevations in blood glucose levels after glucose ingestion.

Aged↗

PubMed1992

Glucose attenuation of paradoxical sleep deficits in old rats.

Glucose administration enhances memory in several amnestic populations, including old humans and rodents. The present experiment demonstrates that glucose also enhances measures of sleep in old rats. Three-hour day-time sleep EEGs were assessed in 3- and 24-month-old rats. The animals received injections of saline or glucose (100, 500, and 1000 mg/kg) on different days in a counter-balanced order. At doses of 100 and 500 mg/kg, glucose augmented the duration of paradoxical sleep bouts and total paradoxical sleep time in old, but not young, rats. Within 2 weeks after the sleep tests, measures of several brain neurotransmitter functions were obtained. Glucose was more effective in enhancing paradoxical sleep in those individual aged rats with high levels of hippocampal choline acetyltransferase and occipital cortex serotonin concentrations than in aged rats with lower levels on these neurochemical measures. The findings suggest that glucose attenuates selective age-related sleep deficits in old rats. More generally, these results add to a growing body of evidence indicating that moderate doses of peripheral glucose can influence a variety of CNS measures.

Aging↗

PubMed1992

Scopolamine-induced deficits in spontaneous alternation performance: attenuation with lateral ventricle injections of glucose.

This experiment determined whether centrally administered glucose can attenuate scopolamine-induced deficits in spontaneous alternation performance. All rats were surgically prepared with indwelling cannulae directed at the lateral ventricle. Thirty min prior to alternation tests, rats received systemic (ip) injections of saline or scopolamine (3 mg/kg). Ten or thirty min prior to training, the rats also received a direct injection into the lateral ventricle of either artificial cerebrospinal fluid (CSF) or glucose (3 micrograms in 1 microliter). Scopolamine significantly impaired spontaneous alternation performance relative to controls. Additional treatment with ICV glucose 30 min, but not 10 min prior to testing, significantly attenuated the scopolamine-induced deficit. These results add support to the view that glucose acts directly on brain systems to attenuate behavioral effects of cholinergic antagonists.

Animals↗

PubMed1992

Impairment of spontaneous alternation performance by an NMDA antagonist: attenuation with non-NMDA treatments.

N-Methyl-D-aspartate (NMDA) receptor antagonists disrupt learning on a variety of tasks. Previous findings indicate that glucose, naloxone, and physostigmine ameliorate learning deficits produced by several treatments. The present experiment examines whether these agents also reverse the amnestic effects of NMDA receptor blockade. Mice were tested for spontaneous alternation performance in a Y-maze. The animals received either saline or the NMDA antagonist, NPC 12626 (35 mg/kg, IP), 50 min prior to testing and received an additional injection of saline, glucose, naloxone, or physostigmine 30 min prior to testing. NPC 12626 significantly decreased alternation scores. Glucose (250 mg/kg), physostigmine (0.01 mg/kg), and naloxone (1 mg/kg) reversed the effects of NPC 12626. Thus, impairments of learning after NMDA receptor blockade share with other amnestic conditions the susceptibility to attenuation by glucose, naloxone, and physostigmine.

Amino Acids↗

PubMed1991

Effects of the novel NMDA antagonist, NPC 12626, on long-term potentiation, learning and memory.

NPC 12626 (2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid), a newly developed drug which crosses the blood-brain barrier, is a competitive antagonist of N-methyl-D-aspartate receptors. In Experiment I, the effects of NPC 12626 on perforant path - dentate gyrus LTP were tested. NPC 12626 (100 mg/kg, i.p.), injected 150 min prior to tetanization, prevented potentiation of the EPSP slope and population spike amplitude. EPSP-spike potentiation was also prevented. Post-tetanus administration was ineffective. In Experiment II, mice were injected with NPC 12626 (35 mg/kg, i.p.) or saline 35 min prior to spontaneous alternation testing. NPC 12626 significantly decreased alternation rates, but did not affect turn bias or the mean delay between arm entries. This pattern of results may reflect impaired learning or memory. In Experiment III, mice were tested on an inhibitory avoidance task. NPC 12626 (35 mg/kg, i.p.), administered before but not after training, significantly impaired performance. When the drug was administered before training as well as before testing, performance was similarly impaired, indicating that the observed deficits were not attributable to state-dependent learning. Pre-test injections were ineffective. Overall, these results support the hypothesis that some forms of learning require the participation of NMDA receptors and that this participation is largely limited to acquisition processes. In addition, these results point to the utility of peripherally administered NPC 12626 as a tool with which to examine the involvement of NMDA receptors in LTP and learning.

Amino Acids↗

PubMed1991

Naloxone modulates the behavioral effects of cholinergic agonists and antagonists.

Peripheral glucose administration enhances memory in rodents and humans. Recent findings suggest that glucose may affect behavior, in part, by augmenting central cholinergic functions and by attenuating central opiate functions. The present experiments examined interactions between an opiate antagonist, naloxone, and cholinergic agents to determine whether the effects would parallel those found with glucose. Three behavioral measures were assessed: tremors, hyperactivity, and spontaneous alternation. Naloxone (1 mg/kg) significantly augmented tremors elicited by physostigmine (0.3 mg/kg). Naloxone (1 mg/kg) also attenuated increases in locomotor activity and impairments in spontaneous alternation performance elicited by scopolamine (1 and 3 mg/kg for activity and alternation measures, respectively). Thus, across three diverse measures, naloxone produced effects similar to those previously reported for glucose. These findings are consistent with the hypothesis that release of cholinergic activity from opiate inhibition may contribute to glucose effects on behavior.

Animals↗

PubMed1991

Glucose effects on mecamylamine-induced memory deficits and decreases in locomotor activity in mice.

Peripheral glucose administration attenuates the effects of muscarinic cholinergic antagonists on several measures, including spontaneous alternation, inhibitory avoidance, and locomotor activity. The present study examined glucose interactions with mecamylamine, a nicotinic cholinergic antagonist, on these measures. Mecamylamine (5 mg/kg, sc) significantly impaired spontaneous alternation performance. Glucose (100 mg/kg, ip) administered with mecamylamine attenuated the impairment. Treatment with hexamethonium (5 and 10 mg/kg, sc), a peripheral nicotinic blocker, did not impair performance. Pretraining treatment with mecamylamine, but not hexamethonium, significantly reduced later retention latencies on inhibitory avoidance tests. Glucose, administered with mecamylamine prior to training, significantly attenuated the impaired test performance. Mecamylamine, but not hexamethonium, significantly decreased locomotor activity. In contrast to the attenuating effects of glucose on the other measures above, glucose administered with mecamylamine potentiated the decreased locomotor activity. These findings demonstrate that glucose influences the behavioral effects of a nicotinic cholinergic antagonist in a manner generally similar to that of muscarinic cholinergic antagonists, and supports previous evidence that circulating glucose interacts with central cholinergic functions.

Animals↗

PubMed1991

Scopolamine- and morphine-induced impairments of spontaneous alternation performance in mice: reversal with glucose and with cholinergic and adrenergic agonists.

Administration of epinephrine and glucose, as well as drugs that influence cholinergic and opiate systems, can enhance or impair memory. The present experiments examined the possibility that peripheral glucose administration might reverse scopolamine- and morphine-induced impairments in a spontaneous alternation task. Mice received all drug administrations 30 min before testing. Scopolamine-induced (3 mg/kg) deficits in alternation performance were reversed by glucose (100 and 250 mg/kg), amphetamine (1 mg/kg), epinephrine, physostigmine, and oxotremorine (each 0.1 mg/kg). Morphine (10 mg/kg) also impaired spontaneous alternation performance, and glucose (100 and 300 mg/kg) reversed this impairment as well. These findings are consistent with the view that central cholinergic systems, possibly under inhibitory opiate regulation, may contribute to glucose and epinephrine effects on memory storage.

Amphetamine↗

PubMed1990

Adrenalectomy-induced memory deficits: role of plasma glucose levels.

Circulating glucose levels regulate memory storage under several conditions. This study examined the contribution of blood glucose levels to the transient memory impairment seen in adrenalectomized rats. Inhibitory (passive) avoidance retention performance, blood glucose levels, and glycemic responses to footshock were tested 1, 2, and 8 days after adrenalectomy. Adrenalectomized animals demonstrated a transient inhibitory avoidance deficit 1 and 2 days after surgery which recovered by 8 days. The adrenalectomy-induced memory deficit was accompanied by decreased resting blood glucose levels. In animals tested 2 days after adrenalectomy, this decrease in baseline blood glucose levels was exacerbated by further reductions, rather than the normal increases, in circulating glucose levels after training. The magnitude of blood glucose increases after glucose injection was decreased in adrenalectomized animals tested 2 days after surgery. Posttraining glucose injections restored the retention performance of animals trained 2 days after adrenalectomy to that of sham-operated animals. These findings suggest that abnormalities in blood glucose regulation may contribute, in part, to the transient memory impairment seen after adrenalectomy. Additionally, the results further implicate blood glucose in the regulation of CNS information processing systems.

Adrenalectomy↗

PubMed1990

Glucose and physostigmine effects on morphine- and amphetamine-induced increases in locomotor activity in mice.

Recent findings indicate that glucose antagonizes several behavioral effects of cholinergic antagonists and augments those of cholinergic agonists. For example, scopolamine elicits increased locomotor activity, an action which is attenuated by glucose and by combined treatment with glucose and physostigmine at doses which are individually without effect. Opiate and catecholamine agonists, such as morphine and amphetamine, also elicit hyperactivity. The present study examined interactions of glucose and physostigmine with morphine- and amphetamine-induced hyperactivity. Mice received saline, morphine (10 mg/kg), or amphetamine (1 mg/kg) 50 min prior to testing, followed by saline, physostigmine (0.01, 0.05, 0.1, or 0.2 mg/kg), or glucose (10, 50, 100, or 500 mg/kg) administered 20 min prior to activity testing in an open field. Physostigmine significantly attenuated both morphine- and amphetamine-induced increases in activity, but higher doses were required to attenuate the effects of amphetamine. Like physostigmine, glucose significantly attenuated morphine-induced activity levels, but unlike physostigmine, glucose did not attenuate amphetamine-induced activity. Thus, the behavioral effects of morphine were more susceptible to modification by physostigmine and glucose than were the effects of amphetamine. The attenuation of morphine-induced hyperactivity demonstrates a similarity between glucose and cholinergic agonists, and also indicates that glucose may inhibit, directly or indirectly, opiate functions. More generally, these findings add to the evidence that circulating glucose levels selectively influence a growing list of behavioral and neurobiological functions.

Amphetamine↗

PubMed1990

Poor blood glucose regulation predicts sleep and memory deficits in normal aged rats.

Poor glucose regulation predicts memory deficits in individual elderly humans. The present experiment determined whether glucose regulation was also related to memory and to sleep in aged rodents. Glucose regulation, inhibitory avoidance, and daytime sleep were assessed in young (3-month-old) and old (24-month-old) rats. Correlations were obtained between glucose regulation and the other variables in individual rats. In old rats, the magnitude of increases in blood glucose levels after glucose injections (500 mg/kg) was inversely correlated with retention of inhibitory avoidance and duration of paradoxical sleep bouts. In young rats, these measures were not significantly correlated. Because the deficits in sleep and memory in aged rats were largely confined to those rats with poor glucose control, peripheral glucose regulation may be a useful biological marker that accompanies cognitive and neurobiological dysfunction during aging.

Aging↗

PubMed1989

Glucose enhancement of performance on memory tests in young and aged humans.

Recent findings indicate that glucose administration enhances memory processes in rodents. This study examined the effects of glucose on memory in humans. After drinking glucose- or saccharin-flavored beverages, college-aged and elderly humans were tested with modified versions of the Wechsler Memory Scale. Beverages and tests were administered in a counter-balanced, crossover design, enabling within subject comparisons. The major findings were: (1) glucose enhanced memory in elderly and, to a lesser extent, in young subjects; and (2) glucose tolerance in individual subjects predicted memory in elderly, but not in young subjects on both glucose and saccharin test days.

Adolescent↗

PubMed1988

Amygdala kindling effects on sleep and memory in rats.

Sleep disturbances accompany the development of amygdaloid-kindled seizures in cats. Some of these sleep deficits resemble those seen in aged rats; these latter changes in sleep patterns are correlated with memory impairments in the aged animals. In the present study, we examined the hypothesis that sleep deficits after kindling may be related to memory impairments. Rats were kindled for 4 weeks (2-2.5 weeks after stage 5 seizures) and were then allowed a one week recovery period. Sleep patterns were assessed through-out the kindling and recovery periods. The animals were then trained on an inhibitory avoidance apparatus and tested for retention 24 h later. Only transient sleep changes occurred during the development of kindling (to stage 5 seizures). However, continued kindling resulted in significant reductions in several sleep measures which remained depressed for at least one week after the termination of the kindling trials. As a group, kindled rats were impaired in retention of the inhibitory avoidance learned response. In kindled animals, retention performance was significantly correlated with total paradoxical sleep, the ratio of paradoxical/total sleep, and paradoxical sleep, the ratio of paradoxical/total sleep, and paradoxical sleep bout duration. These correlations are consistent with the view that deficits in paradoxical sleep may be related to deficits in some forms of memory.

Amygdala↗