Search Results - (Author, Cooperation:J. Feldon)

2013-03-02

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Animals ; Cytokines/immunology ; Disease Models, Animal ; Female ; Humans ; Mental Disorders/*immunology ; Mice ; Mice, Inbred C57BL ; Poly I-C/immunology/pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects/*immunology/virology ; Puberty/*immunology ; Stress, Physiological/*immunology

1460-9568

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Four separate cohorts of rats were employed to examine the effects of cytotoxic retrohippocampal lesions in four spatial memory tasks which are known to be sensitive to direct hippocampal damage and/or fornix-fimbria lesions in the rat. Selective retrohippocampal lesions were made by means of multiple intracerebral infusions of NMDA centred on the entorhinal cortex bilaterally. Cell damage typically extended from the lateral entorhinal area to the distal ventral subiculum. Experiment 1 demonstrated that retrohippocampal lesions spared the acquisition of a reference memory task in the Morris water maze, in which the animals learned to escape from the water by swimming to a submerged platform in a fixed location. In the subsequent transfer test, when the escape platform was removed, rats with retrohippocampal lesions tended to spend less time searching in the appropriate quadrant compared to controls. Experiment 2 demonstrated that the lesions also spared the acquisition of a working memory version of the water maze task in which the location of the escape platform was varied between days. In experiment 3, both reference and working memory were assessed using an eight-arm radial maze in which the same four arms were constantly baited between trials. In the initial acquisition, reference memory but not working memory was affected by the lesions. During subsequent reversal learning in which previously baited arms were now no longer baited and vice versa, lesioned animals made significantly more reference memory errors as well as working memory errors. In experiment 4, spatial working memory was assessed in a delayed matching-to-position task conducted in a two-lever operant chamber. There was no evidence for any impairment in rats with retrohippocampal lesions in this task. The present study demonstrated that unlike direct hippocampal damage, retrohippocampal cell loss did not lead to a general impairment in spatial learning, implying that the integrity of the retrohippocampus and/or its interconnection with the hippocampal formation is not critical for normal hippocampal-dependent spatial learning and memory. This outcome is surprising for a number of current hippocampal theories, and suggests that other cortical as well as subcortical inputs to the hippocampus might be of more importance, and further raises the question regarding the functional significance of the retrohippocampal region.Introduction

Electronic Resource

0022-3956

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Medicine

Electronic Resource

1432-1106

Septum ; Hippocampus ; Theta ; Cholinesterase

Springer Online Journal Archives 1860-2000

Medicine

Summary Recordings were made of spontaneous hippocampal theta activity in free-moving rats, before and after a variety of lesions. Three recording sites were used to monitor activity in the dorsal hippocampus, the ventral hippocampus, or close to the site of the hippocampal flexure. Electrolytic lesions were made in the medial septal area or the dorso-lateral septal area; surgical transections were made of the fimbria or dorso-medial area of the fornix. Following lesions restricted to the medial septal area, theta was abolished throughout the hippocampus; after lesions restricted to the dorso-lateral septal area theta was retained. Fimbria lesions abolished theta in the ventral, but not the dorsal hippocampus; dorso-medial fornix lesions abolished it in the dorsal, but not the ventral, hippocampus. In some subjects the hippocampal formation was subsequently stained for cholinesterase: cholinesterase staining loss was generally associated with theta loss, but this was not clear at the flexure recording site. It was confirmed that theta is dependent upon the integrity of the medial septal area. It was concluded that damage to hippocampal afferents from the septum does abolish theta, while damaging the feedback efferents does not.

Electronic Resource

1432-1106

Partial reinforcement extinction effect ; Hippocampectomy ; Fimbria ; Extinction

Springer Online Journal Archives 1860-2000

Medicine

Summary Rats were trained to run in an alley for food reward given on every trial (continuous reinforcement, CR) or on a random 50% of trials (partial reinforcement, PR) and were then extinguished. Sham-operated controls showed the usual partial reinforcement extinction effect (PREE), i.e., PR-trained animals were more resistant to extinction than CR-trained animals. The PREE was abolished by hippocampectomy, which increased resistance to extinction in CR-trained rats and decreased it in PR-trained rats. Bilateral fimbria section had no effect on resistance to extinction in either condition. These results are discussed in the light of theories of hippocampal function and the anatomy of septohippocampal connections.

Electronic Resource

0163-1047

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Psychology

Electronic Resource

0163-1047

Elsevier Journal Backfiles on ScienceDirect 1907 - 2002

Biology

Psychology

Electronic Resource

1432-2072

Chronic amphetamine ; Latent inhibition ; Conditioned suppression ; Schizophrenia ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract The animal amphetamine model of schizophrenia has been based primarily on stereotyped behavior. The present study sought to demonstrate an amphetamine-induced deficit in attentional processes. To this end, the effects of acute and chronic (14 days) 1.5 mg/kg dl-amphetamine administration on the ability of rats to ignore irrelevant stimuli were examined using the paradigm of latent inhibition (LI) in a conditioned emotional response (CER) procedure. The procedure consisted of three stages: pre-exposure, in which the to-be-conditoned stimulus, tone, was presented without being followed by reinforcement; acquisition, in which the pre-exposed tone was paired with shock; and test, in which LI was indexed by animals' suppression of licking during tone presentation. Experiment 1 showed that chronic but not acute treatment abolished LI. Experiment 2 showed that animals receiving chronic amphetamine pretreatment but pre-exposed and conditioned without the drug, exhibited normal LI. In Experiment 3, animals which received chronic amphetamine pretreatment and were pre-exposed under the drug but conditioned without it, also showed normal LI. The implications of these results for the animal amphetamine model of schizophrenia are discussed.

Electronic Resource

1432-2072

Chlordiazepoxide ; Metrazol ; Audiogenic seizures ; Resistance to extinction ; Resistance to punishment ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract Three experiments were carried out to test the long-term behavioral effects of 12 days administration of CDP (5 mg/kg/day) in rats. In the first two experiments, 4 weeks after the end of drug administration (CDP or placebo), and after 2 weeks of training to run a straight alley for food reward, animals were tested in extinction, i.e., following omission of reward (Expt. 1) or with punishment, i.e., 0.3 mA electric shock in addition to the food reward (Expt. 2). Drug-treated animals showed significantly increased resistance to extinction and to punishment compared with controls. In the third experiment, 10 weeks after drug administration, animals were exposed to 60 s of intense noise to induce audiogenic seizures. The convulsant metrazol was injected 5 min prior to successive sessions (10 min apart) with doses starting at 10 mg/kg and increased by 10 mg/kg each session up to 40 mg/kg. Drug-treated animals were significantly less susceptible to seizures than their placebo controls. These results suggest that chronic benzodiazepine treatment causes long-term neurochemical changes which are responsible for the observed behavioral effects.

Electronic Resource

1432-2072

Chlordiazepoxide ; Punishment ; Conditioned suppression ; Rats

Springer Online Journal Archives 1860-2000

Medicine

Abstract Rats were trained to lever press for sucrose on a random interval (RI) 64-s schedule. During a 55 min session there were four 3 min “intrusion periods” signalled by a flashing house-light. In experiment 1 there were two groups matched for baseline response rate. During the intrusion periods one group received response-independent footshock on an independent RI64 schedule; the other group received responsecontingent shock on this schedule. Shock intensity was varied for each rat to match degree of response suppression between the two groups. Chlordiazepoxide HCl (CDP) in doses 0.5–5 mg/kg alleviated response suppression equally in both groups. Experiment II followed the same procedure, except that all animals had the same shock intensity, producing greater response suppression in the response-contingent shock groups. CDP alleviated response suppression more in the response-contingent shock groups, significantly so at 5 mg/kg, nonsignificantly at 1 mg/kg. These results suggest that previous reports that CDP differentially alleviates the response suppression produced by response-contingent shock are an artefact of rate dependency.

Electronic Resource

1432-2072

Spontaneous alternation ; Amylobarbitone ; Scopolamine ; Septal lesions ; Hippocampal theta rhythm

Springer Online Journal Archives 1860-2000

Medicine

Abstract Sodium amylobarbitone, scopolamine and septal and hippocampal lesions all reduce spontaneous alternation. However, septal lesions appear to reduce alternation of places more than body turns, while the reverse is true for hippocampal lesions. The present experiments tested the effects of amylobarbitone and scopolamine on place and body turn alternation. Medial and lateral septal lesions were also tested. The former block hippocampal theta rhythm but the latter do not. Amylobarbitone (20 mg/kg, IP) reduced alternation of body turns to chance levels when this was present in control animals, but it did not affect alternation of place. Scopolamine (1.2 mg/kg, IP) reduced both body turn alternation and place alternation. Medial septal lesions produced significant perseveration of body turns and produced a non-significant reduction in place alternation. Lateral septal lesions, tested in a small number of animals, did not appear to affect alternation. The treatments thus reduce spontaneous alternation in differing ways which can in part be accounted for in terms of their differing effects on hippocampal theta rhythm.

Electronic Resource

1432-1106

Septum ; Ibotenic acid ; Resistance to extinction ; Partial reinforcement ; Rats

Springer Online Journal Archives 1860-2000

Medicine

Summary Rats were given sham operations, vehicle injections, or injections of the axon-sparing excitotoxin ibotenic acid into the septum. In Experiment 1, behavioural testing commenced 16 days after the operation; in Experiment 2 behavioural testing commenced following testing on another task, 31 days after the operation. The rats were trained to run in an alley for food reward given on every trial (Continuous Reinforcement, CR) or on a random fifty percent of trials (Partial Reinforcement, PR) and then the running response was extinguished. All the experimental groups showed the normal partial reinforcement extinction effect (PREE) in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. However the rats with ibotenic acid lesions also showed a significant decrease in resistance to extinction regardless of training condition. The same pattern of results was seen at each of the two post-operative testing times. The results were thus readily replicable, and entirely unlike previous reports of the behavioural effects on this task of conventional septal lesions of equivalent size. In Experiment 3, neurochemical analysis of the hippocampus in rats with ibotenic acid-induced lesions demonstrated that choline acetyl-transferase levels were reduced to the same extent as in rats with comparable conventional lesions.

Electronic Resource

1432-1106

Hippocampus lesion ; Partial reinforcement ; Delay of reinforcement ; Inter-trial interval ; Inter-event interval ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Summary Two experimental procedures were employed to establish the reason why hippocampal lesions apparently block the development of tolerance for aversive events in partial reinforcement experiments, but do not do so in partial punishment experiments. Rats were trained to run in a straight alley following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO), and resistance to extinction was assessed following differing acquisition conditions. In Experiment 1 a 4–8 min inter-trial interval (ITI) was used. Either every acquisition trial was rewarded immediately (Continuous Reinforcement, CR), or only a randomly selected half of the trials were immediately rewarded, the reward being delayed for thirty seconds on the other trials (Partial Delay, PD). This delay procedure produced increased resistance to extinction in rats in all lesion groups. In Experiment 2 the ITI was reduced to a few seconds, and rats were trained either on a CR schedule, or on a schedule in which only half the trials were rewarded (Partial Reinforcement, PR). This form of partial reinforcement procedure also produced increased resistance to extinction in rats in all lesion groups. It thus appears that hippocampal lesions only prevent the development of resistance to aversive events when the interval between aversive and subsequent appetitive events exceeds some minimum value.

Electronic Resource

1432-1106

Nucleus accumbens ; Electrolytic lesion ; PREE ; Locomotion

Springer Online Journal Archives 1860-2000

Medicine

Summary The partial reinforcement extinction effect (PREE) refers to the increased resistance to extinction observed in animals trained on a partial reinforcement (PR) schedule compared with those trained on a schedule of continuous reinforcement (CR). It has been suggested that the PREE is dependent upon the integrity of the septo-hippocampal system, but recent evidence has indicated that the role originally proposed for the lateral septal nucleus may in fact be subserved by the nucleus accumbens. Experiment I therefore tested the effects of electrolytic lesions of the nucleus accumbens on the PREE. These lesions abolished the PREE, the abolition resulting from a decreased rate of extinction in the lesion CR rats coupled with an increased rate of extinction in the PR rats. These results clearly implicate the nucleus accumbens in the development of the PREE, and suggest that theoretical models of the PREE based simply upon consideration of septohippocampal interactions need radical revision. The lesion also enhanced running speeds in acquisition in both the CR and the PR groups. Experiment II therefore assessed spontaneous locomotor activity and the locomotor response to amphetamine challenge at two doses. The lesion produced no increase in spontaneous locomotion; an enhanced increase in response to 1 mg/kg amphetamine; and no changes in the stereotyped behaviours induced by 10 mg/kg amphetamine.

Electronic Resource

1432-1106

Subiculum ; Postcommissural fornix ; Precommissural fornix ; Resistance to extinction ; Partial reinforcement ; Rats

Springer Online Journal Archives 1860-2000

Medicine

Summary Rats were trained to run in an alley for food reward given on every trial (Continuous Reinforcement, CR) or on a random fifty percent of trials (Partial Reinforcement, PR) and the running response was then extinguished. Sham Operated controls showed the normal partial reinforcement extinction effect (PREE) in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. The PREE was abolished by a knife cut placed at the base of the lateral septum to interrupt ventral subicular fibres destined for the ventral striatum. This outcome stemmed purely from a decrease in resistance to extinction in the lesion PR group. A larger lesion that also sectioned the dorsal subicular pathway in the descending columns of the fornix left the PREE intact, though there were some signs of a reduction in its size primarily due to increased resistance to extinction in the lesion CR group. We conclude that previous reports demonstrating reduction or abolition of the PREE following conventional total septal or lateral septal lesions, may have achieved their results through damage to subicular fibres en passage through the septum.

Electronic Resource

1432-1106

Fornix-fimbria ; Partial reinforcement ; Resistance to extinction

Springer Online Journal Archives 1860-2000

Medicine

Summary Rats were trained to run in an alley for food reward given on every trial (continuous reinforcement, CR) or on a random 50% of trials (partial reinforcement, PR) and were then extinguished. Sham-operated controls showed the normal partial reinforcement extinction effect (PREE), in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. The PREE was significantly reduced by lesions of the fornix-fimbria. The reduction was largely a consequence of a reduction in resistance to extinction in PR-trained rats with fimbria-fornix lesions. These results are discussed in the light of other experiments that have studied disconnections in the septo-hippocampal system.

Electronic Resource

1432-1106

Hippocampus ; Subiculum ; Partial reinforcement extinction effect ; Partial reinforcement acquisition effect ; Entorhinal cortex ; botenate

Springer Online Journal Archives 1860-2000

Medicine

Summary Intracerebral injections of ibotenate were used to produce, in rats, extensive cell loss in the hippocampus and dentate gyrus (complete hippocampal, CH), in the CH plus subiculum (SUB + CH), or in the subiculum plus entorhinal cortex (SUB + EC). These rats and sham-operated controls were trained to run in a straight alley for food reward delivered on a continuous (CR) or partial (PR) reinforcement schedule. In controls PR training gave rise to the well-known partial reinforcement extinction effect (PREE), i.e., greater resistance to extinction than that observed in CR-trained animals. Previous work had shown that large aspiration lesions of the hippocampal formation eliminate the PREE by increasing resistance to extinction in CR-trained animals and decreasing resistance to extinction in PR-trained animals. In the present experiments the PREE survived CH lesions, which increased resistance to extinction in both CR and PR training conditions; these effects were observed in the start and run (but not goal) sections of the alley. In contrast, subicular cell loss (in both SUB + CH and SUB + EC groups) abolished the PREE (but in the goal section only) by increasing resistance to extinction in the CR condition and decreasing resistance to extinction in the PR condition. In addition, some of the effects of PR training on start and run speeds during acquisition were altered by the CH and SUB + CH lesions. These results confirm previous data showing that the hippocampal formation plays a role in mediating the behavioural effects of PR training, but require modification of the model previously proposed to account for these data.

Electronic Resource

1432-1106

Key words Entorhinal cortex ; Subiculum ; Retrohippocampus ; Latent inhibition ; Partial reinforcement extinction effect ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Experiment 1 assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.

Electronic Resource

1432-1106

Retrohippocampal cortex ; Locomotion ; Amphetamine ; Ventral striatum ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract The present experiment assessed the locomotor response to a low dose (1 mg/kg) of systemic gemd-amphetamine in rats with cytotoxic lesions of the retrohippocampus (entorhinal and extra-subicular cortices), compared with vehicle-operated shams and unoperated controls. Under spontaneous and saline conditions, both the sham and the lesioned animals were more active than unoperated controls, and they did not differ from each other. Systemic gemd-amphetamine produced increased locomotion in all groups, but this effect was potentiated in animals with retrohippocampal lesions; two control groups did not differ from each other in their response to the drug. The present results are consistent with the suggestion that cell loss within the retrohippocampal region could affect the functional response of nucleus accumbens to amphetamine. The results are discussed in terms of the interaction between the retrohippocampus and nucleus accumbens in the control of mesolimbic dopamine release and the possible implications for schizophrenia.

Electronic Resource

1432-2072

dl-Amphetamine ; Continuous reinforcement ; Partial reinforcement ; Resistance to extinction ; Rat

Springer Online Journal Archives 1860-2000

Medicine

Abstract The effects of amphetamine administration on the partial reinforcement extinction effect (PREE) at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested inextinction. dl-Amphetamine 1.5 mg/kg was administered in a 2×2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction. In contrast, amphetamine administered in acquisition abolished the PREE irrespective of drug treatment in extinction. In addition, amphetamine administered in extinction alone increased resistance to extinction in PRF animals.

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