Biomedical subjects

J Feldon

Publications and source records attributed to J Feldon.

185 records · Page 11Linked to original sources

PubMed1977

The role of the septo-hippocampal system and its noradrenergic afferents in behavioural responses to none-reward.

Our experiments were designed with two purposes: (i) to examine the effects on one behaviour of differing interventions in the septo-hippocampal system; (ii) to compare these effects with those of minor tranquillizers. The behaviour studied (in rats) is extinction in the alley after continuous (CRF) or partial (PRF) reinforcement. Minor tranquillizers and large septal lesions produce three effects: (1) resistance to extinction is increased after CRF; (2) resistance to extinction is decreased after PRF; (3) the partial reinforcement extinction effect (PREE) is abolished. Small septal lesions fractionate this syndrome: either effect (1) or an actual increase in the size of the PREE is produced by medial septal lesions abolishing hippocampal theta; effects (2) and (3), but not (1), are produced by lateral septal lesions sparing theta. Dorso-medial fornix section, abolishing theta, reproduces the effects of medial septal lesions. Fimbrial section, sparing theta, reproduces some of the effects of lateral septal lesions. Minor tranquillizers produce a rise in the threshold for septal driving of hippocampal theta specifically at 7.7 Hz. This effect is reproduced by blockade of noradrenergic transmission or destruction of the dorsal noradrenergic bundle with 6-hydroxydopamine. This lesion reproduces all three behavioural changes listed above. These results suggest a model for the role of the septo-hippocampal system and its noradrenergic inputs in the PREE. This model is compared with other approaches to the septo-hippocampal system.

Afferent Pathways↗

PubMedDate not supplied

Immunization with cholinergic cell bodies induces histopathological changes in rat brains.

We have previously shown that sera from patients with Alzheimer's disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergic Torpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization with Torpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.

Animals↗

PubMedDate not supplied

Early social isolation, but not maternal separation, affects behavioral sensitization to amphetamine in male and female adult rats.

Early life stressful manipulations, such as maternal separation (MS) or social isolation (SI), can influence the neurobiological development of rats and alter the response of adult animals to drugs of abuse. The present study examined the acute and sensitized behavioral responses (locomotor activity (LMA) and stereotypy) induced by amphetamine after MS or SI in male and female rats. In addition, the hypothesis that the combination of SI and MS could lead to additional effects on the behavioral response to amphetamine was tested. After the repetitive, intermittent administration of 1.5 mg/kg D-amphetamine over five consecutive days, the behavioral expression of sensitization to a challenge injection was assessed following a 2-day withdrawal period. In both sexes, MS and SI did not alter the acute locomotor activating effects of amphetamine as measured in the open-field environment after the first administration of the drug. Whereas SI altered the expression of sensitization to amphetamine in both sexes, MS did not affect it. Finally, in none of the behavioral variables measured did MS and SI interact to further modify the behavioral profile of the animals. The present results suggest that a postweaning manipulation of the environment (SI) is more effective than a preweaning manipulation (MS) in modifying the expression of sensitization to amphetamine.

Aging↗

PubMedDate not supplied

Gender- and age-dependent differences in latent inhibition following pre-weaning non-handling: implications for a neurodevelopmental animal model of schizophrenia.

Latent inhibition (LI) refers to retarded conditioning to a stimulus as a consequence of its prior nonreinforced pre-exposure, and is considered to index the capacity of an organism to ignore irrelevant stimuli. LI disruption has received increasing attention as an animal model of the widely described attentional deficit of schizophrenia, consisting of an inability to ignore irrelevant stimuli. The present experiments investigated the effects of infantile manipulations on the development of LI. Male and female rats handled or nonhandled in infancy (days 1-22), were tested at 3 and 16 months. Young handled animals had lower emotional reactivity than nonhandled, and this difference persisted in females at 16 months. At 3 months. LI, poorer conditioning of stimulus pre-exposed as compared to nonpre-exposed rats, was obtained in handled and nonhandled females, as well as in handled males, but was absent in nonhandled males. This pattern changed at 16 months: both nonhandled males and females failed to show LI. These gender- and age-dependent effects of pre-weaning manipulations on LI loss may provide an animal parallel to the susceptibility of young adult males to schizophrenia and the attenuation of gender differences in long-term outcome schizophrenia.

Aging↗

PubMedDate not supplied

Induction of cognitive deficits by immunization with cholinergic cell bodies: the influence of age and integrity of the blood-brain barrier.

We have recently shown that prolonged immunization of young rats for one year with cholinergic cell bodies (perikarya, PK) purified from Torpedo electric lobe results in the accumulation of IgG in specific brain areas such as the hippocampus and induces behavioral deficits in spatial orientation and short term memory /1, 7/. We presently studied the rate of development of the cognitive deficit in older (12 months old) Sprague Dawley rats which were immunized for periods of up to one year with either Torpedo cholinergic PK or adjuvant (controls). T-maze alternation and Morris swim maze tests revealed a small deficit in the performance of the PK immunized rats after 6 months whereas significant deficits were observed after 12 months of immunization. These results suggest that the duration of immunization is a more significant factor than the age of the animals in the development of the behavioral deficit. In order to examine whether permeability of the blood-brain barrier to IgG influences the rate of development of the cognitive deficit, we disrupted the blood-brain barrier of PK immunized rats by hypercapnia. This treatment repeated weekly for 2 months was found not to accelerate the rate of appearance of deficits in performance of the rats in the T-maze alternation and Morris swim test. These results suggest that penetration of IgG via the blood-brain barrier does not determine the rate of appearance of the cognitive deficits.

Age Factors↗