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The cellular basis of depressive disorders is poorly understood. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive(More)
In former studies, we found evidence for the hypothesis that withdrawal of negative reinforcement presents a major source for stress and despair. Specifically, the removal of a hidden platform in the water maze induced extinction of previously reinforced escape behavior and behavioral immobility, indicative of "despair", which also correlated with indices(More)
In 28- to 30-month-old rats, in vitro short-term and long-term potentiation (STP and LTP) were measured in area CA1 of the hippocampus in seven superior and seven inferior learners, that were selected from a pool of 40 rats based on water maze escape performance over a period of 9 days. The aim was to examine whether levels of STP and LTP could account for(More)
Your paper may be eligible for our advance online publication (AOP) programme. In this programme, your paper will be published online on Nature's website at www.nature.com/nature as soon it is typeset and your proof corrections returned. It will be published in print as soon afterwards as space is available. The two versions of the paper are identical. Our(More)
The present study investigated the effect of a single, anesthetic dose of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, on behavioral despair, an animal model of depression. Separate groups of male Wistar rats injected with an anesthetic dose of ketamine (160 mg/kg ip) and tested 3, 7, or 10 days later showed(More)
Striatal parameters were assessed for their relevance to age-related behavioural decline. Forty aged rats (28-30 months) were tested in the water maze and open field. Of these, seven superior and seven inferior learners were compared with each other in terms of levels of in vitro short- and long-term potentiation (STP and LTP), and gene expression of(More)
The bed nucleus of the stria terminalis (BNST) was lesioned in adult male Wistar rats (n = 9) and its involvement in coping behavior during forced swim stress examined. Rats remain immobile longer in the second of two swim tests, a phenomenon known as learned despair. Results revealed that, compared to sham-operated controls (n = 8), BNST-lesioned animals(More)
Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have(More)
The absence or loss of rewards or reinforcers holds a major role in the development of depression in humans. In spite of the prevalence of extinction-induced depression (EID) in humans, few attempts have been made to establish animal models thereof. Here we present the concept of extinction-related depression and summarize the results of two sets of studies(More)
We have previously reported that extinction of escape behavior in the water maze due to the removal of the platform coincided with the development of behavioral "despair" in aged and adult rats, as assessed by immobility. The present study examines further predictions derived from the hypothesis that the withholding of reinforcement induces behaviors akin(More)