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P E Gilbert

Publications and source records attributed to P E Gilbert.

14 recordsLinked to original sources
PubMed2001

Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1.

This study presents a double dissociation between the dentate gyrus (DG) and CA1. Rats with either DG or CA1 lesions were tested on tasks requiring either spatial or spatial temporal order pattern separation. To assess spatial pattern separation, rats were trained to displace an object which covered a baited food-well. The rats were then allowed to choose between two identical objects: one covered the same well as the sample phase object (correct choice), and a second object covered a different unbaited well (incorrect choice). Spatial separations of 15-105 cm were used to separate the correct object from the incorrect object. To assess spatial temporal order pattern separation, rats were allowed to visit each arm of a radial eight-arm maze once in a randomly determined sequence. The rats were then presented with two arms and were required to choose the arm which occurred earliest in the sequence. The choice arms varied according to temporal separation (0, 2, 4, or 6) or the number of arms that occurred between the two choice arms in the sample phase sequence. On each task, once a preoperative criterion was reached, each rat was given either a DG, CA1, or control lesion and then retested. The results demonstrated that DG lesions resulted in a deficit on the spatial task but not the temporal task. In contrast, CA1 lesions resulted in a deficit on the temporal task but not the spatial task. Results suggest that the DG supports spatial pattern separation, whereas CA1 supports temporal pattern separation.

Animals↗
PubMed2000

Testing neural network models of memory with behavioral experiments.

In recent years, a number of computational neural networks have been proposed aimed at describing memory functions associated with different subregions of the hippocampus, namely dentate gyrus, CA3 and CA1. Recent evidence suggests that indeed specific subregions of the hippocampus may subserve different computational functions, such as spatial and temporal pattern separation, short-term or working memory, pattern association, and temporal pattern completion.

Animals↗
PubMed1998

Memory for spatial location: role of the hippocampus in mediating spatial pattern separation.

A paradigm based on measuring short-term memory for spatial location information as a function of spatial similarity between distal cues was developed to examine the role of pattern separation in the modulation of short-term memory for spatial information. A delayed-match-to-sample for spatial location task using a dryland version of the Morris water maze was used to assess spatial pattern separation in male Long-Evans rats. In the sample phase, animals were trained to displace an object that covered a baited food well in one of 15 spatial locations along a row of food wells perpendicular to a start box. In the ensuing choice phase, the animal was allowed to choose between two objects identical to the sample phase object. One covered the same baited food well as did the object in the study phase (correct choice), and another foil object (incorrect choice) covered a different unbaited food well along the row of wells. Five spatial separations were randomly used to separate the correct object from the foil object. After reaching a criterion before the operation, animals were given either hippocampal or cortical control lesions. In trials after the operation, control animals matched their performance before the operation across all spatial separations. In contrast, hippocampal-lesioned animals displayed impairments across all spatial separations with the exception of the longest (105 cm) spatial separation. The results suggest that the hippocampus may serve to separate incoming spatial information by temporarily storing one place separate from another. It is proposed that hippocampal lesions decrease efficiency in pattern separation, resulting in impairments in trials with increased spatial similarity among working-memory representations.

Animals↗
PubMed1987

An analysis of naltrexone precipitated abstinence in morphine-dependent chronic spinal dogs.

Graded doses of naltrexone (0.31, 1.125, 5.0, 20.0 and 80.0 micrograms/kg) were administered to five beagle-type dogs dependent on increasingly large stabilization doses of morphine (0.5, 1.0, 2.0, 4.0, 8.0, 16.0 and 24.0 mg/kg/day) and the intensity of precipitated abstinence (PAS) was determined by a previously developed scoring system. A complete crossover design was executed with all dogs receiving all doses of both naltrexone and morphine. The data were analyzed using a two-way analysis of variance (dogs and treatments). Treatment variance was partitioned into a regression and residual component. A mathematical model for relating the intensity of abstinence (PAS) to the concentrations of morphine and naltrexone was developed using the law of mass action and assuming that the degree of morphine physical dependence is related directly to the number of mu receptors occupied by morphine and the intensity of PAS is proportional to the number of receptors from which morphine is displaced by the antagonist. Using the mathematical model the deviations of the observed values from the calculated values were minimized using an iterative curve-fitting procedure which varied the values of the dissociation constants of morphine (KA) and naltrexone (KB) and the activity coefficient for morphine (alpha). The analysis of variance showed that the treatment effect was significant and that the regression accounted for most of this variance. The values which provided the best fit were: KA, 1.58 mg/kg; KB, 0.95 microgram/kg; and alpha, 245.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Tolerance to and physical dependence on N-allylnormetazocine (NANM) in chronic spinal dogs.

Six female chronic spinal dogs were administered N-allylnormetazocine (NANM) chronically by the intravenous route starting at 0.3 mg/kg/day. The dose was escalated to a stabilization dose of 10 mg/kg/day. The dogs became tolerant to NANM's ability to produce canine delirium and its anorexigenic and respiratory stimulant effects. Naltrexone increased the amplitude of the flexor reflex and pulse rate in the body temperature, pupillary constriction, bradycardia and tachypnea. Appetite was decreased and weight was lost. These data indicate that chronic administration of NANM produces tolerance and a unique type of physical dependence. Some changes produced by chronically administered NANM were naltrexone antagonizable, others were not suggesting that NANM may have several mechanisms of action.

Animals↗
PubMed1978

The pharmacology of thebaine in the chronic spinal dog.

The effects of thebaine were studied in nondependent and morphine-dependent chronic spinal dogs as well as in chronic spinal dogs receiving thebaine chronically. Thebaine did not produce any morphine-like effects in nondependent dogs nor did it precipitate an abstinence syndrome in morphine-dependent dogs. Large doses of naltrexone precipitated a mild abstinence syndrome in dogs receiving thebaine chronically; however, no withdrawal abstinence syndrome was observed after abrupt withdrawal. Thebaine is not a morphine-like drug, nor does it produce appreciable physical dependence in the dog.

Animals↗
PubMed1976

Sigma effects of nalorphine in the chronic spinal dog.

The effects of graded doses of nalorphine and morphine were studied in nondependent chronic spinal dogs. Morphine and low doses of nalorphine produced behavioral changes characterized by indifference, whereas the largest dose of nalorphine produced canine delirium indistinguishable from that produced by SKF-10, 047 or cyclazocine. Nalorphine depressed the flexor reflex; however, a plateau was observed. The data suggest that nalorphine is a partial agonist of the kappa type and a sigma agonist in addition to being a competitive antagonist at the mu receptor, and further, that the dysphoric and hallucinogenic effects of nalorphine-like drugs are due to their sigma activity.

Animals↗
PubMed1976

The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog.

Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.

Animals↗
PubMed1976

The effects of morphine and nalorphine-like drugs in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog.

A series of morphine-like and nalorphine-like drugs were studied in the nondependent, morphine-dependent and cyclazocine-dependent chronic spinal dog. In the nondependent dog, three profiles of activity were found which could be utilized to distinguish between morphine, WIN 35, 197-2 and cyclazocine. Propiram, a prototypic partial agonist of the morphine type, produced morphine-like effects in nondependent dogs and both precipitated and suppressed abstinence in cyclazocine-dependent dogs as was needed to precipitate abstinence in morphine-dependent dogs. WIN 35, 197-2, a strong agonist in the guinea-pig ileum which has been shown to be resistant to antagonism by naloxone, neither precipitated nor suppressed morphine abstinence but suppressed cyclazocine abstinence. In the nondependent dog, it depressed the flexor reflex but not skin twitch reflex. Cyclazocine altered reflex activity much like WIN 35, 197-2 but produced tachycardia, tachypnea, mydriasis and canine delirum. The morphine and cyclazocine precipitated and withdrawal abstinence syndromes were qualitatively different. Twenty times as much naltrexone was needed to precipitate abstinence in morphine-dependent dogs. Nalorphine both precipitated and suppressed cyclazocine abstinence and appeared to be a partial agonist of the nalorphine-type. Morphine suppressed the cyclazocine abstinence syndrome. Cross-tolerance was not observed in ketocyclazocine-dependent dogs. These data are consistent with the hypothesis that there are strong and partial agonists of the mu and kappa types, and further, that physical dependence on morphine and cyclazocine is mediated through different receptors. WIN 35, 197-2 appears to be a pure strong agonist of the kappa type. Cyclazocine is a mu antagonist and mixed kappa and sigma agonist.

Animals↗
PubMed1975

The degradation of polychlorinated biphenyls by micro-organisms.

An investigation is described concerning the effects of two micro-organism cultures on single compounds and multi-component mixtures of polychlorinated biphenyls (PCBs). Several low chlorine PCB compounds can be degraded easily with these cultures and, in favourable circumstances, some compounds containing up to six chlorine atoms per molecule can be degraded. In certain multi-component commercial mixtures some PCB compounds are degraded more readily than if present singly. The significance of this is discussed, particularly the fact that work on single compounds does not enable predictions to be made about the behaviour of commercial mixtures in the enviroment. Some tentative explanations are suggested for the behavious of the mixtures exposed to these cultures.

Biodegradation, Environmental↗
PubMed1975

Antagonism of the convulsant effects of heroin, d-propoxyphene, meperidine, normeperidine and thebaine by naloxone in mice.

Naloxone antagonized convulsions produced by tail vein infusions of d-propoxyphene, heroin, meperidine, normeperidine and thebaine in mice in a dose-related manner. Pretreatment with naloxone (60 mg/kg i.p.) produced a 200 percent increase of the dose of d-propoxyphene or heroin needed to produce a seizure. A 40 percent increase in the convulsant dose of meperidine was observed after naloxone pretreatment (30 mg/kg i.p.). Naloxone (15 mg/kg i.p.) produced a 30 percent increase in the convulsant dose of normeperidine; however, larger doses of naloxone did not produce any further increase in the convulsant dose of either normeperidine or meperidine. Larger doses of naloxone were needed to antagonize convulsions produced by thebaine. Heroin, d-propoxyphene and meperidine produced nonlethal clonic seizures, whereas normeperidine and thebaine produced tonic-clonic seizures which were followed by death. These data suggest that there may be two mechanisms by which narcotic analgesics and their congeners produce convulsions.

Animals↗
PubMedDate not supplied

A comparison of THC, nantradol, nabilone, and morphine in the chronic spinal dog.

Morphine and delta 9-tetrahydrocannabinol (THC) have been shown to have certain pharmacologic characteristics in common. Among these are antinociception, hypothermia, and the suppression of precipitated abstinence in morphine-dependent rats. In the present study the effects of morphine were compared with the effects of THC and two synthetic cannabinoids, nantradol and nabilone, in both nondependent and morphine-dependent chronic spinal dogs. Single doses of THC, nantradol, and nabilone depressed the flexor and skin twitch reflexes and had a calming effect after intravenous infusion. These effects are similar to those of morphine. Morphine, nantradol, and nabilone, but not THC, depressed rectal temperature. Unlike morphine, however, the cannabinoids produced mydriasis and an increased startle response, and these effects were not antagonized by naltrexone. THC, nantradol, and nabilone suppressed withdrawal abstinence in 40-hour and maximally abstinent morphine-dependent chronic spinal dogs. The results suggest that THC, nantradol, and nabilone share some properties with morphine since they increased the latency of the skin twitch reflex and suppressed withdrawal abstinence. It is doubtful, however, that these actions of the cannabinoids are mediated through opioid receptors since they were not antagonized by naltrexone.

Animals↗