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Cited by 404Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorTryptophan and brain disorders

Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome

Heidbreder, C.A, Weiss, I.C, Domeney, A.M, Pryce, C, Homberg, J, Hedou, G, Feldon, J, Moran, M.C +1 more·2000·Neuroscience
DOI 10.1016/s0306-4522(00)00336-5
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Abstract

Rearing rats in isolation has been shown to be a relevant paradigm for studying early life stress and understanding the genesis of depression and related affective disorders. Recent studies from our laboratory point to the relevance of studying the social isolation syndrome as a function of home caging conditions. Accordingly, the present series of experiments assessed the contribution of each condition to the expression of the prepulse inhibition of the acoustic startle, food hoarding and spontaneous locomotor activity. In addition, ex vivo neurochemical changes in the brains of isolated and grouped rats reared either in sawdust-lined or in grid-floor cages were determined by measuring dopamine and serotonin as well as their major metabolites in a "psychosis circuit" that includes mainly the hippocampus and selected hippocampal efferent pathways projecting towards the anterior cingulate and infralimbic cortices, nucleus accumbens, dorsolateral caudate nucleus, amygdala and entorhinal cortex. The results of the present study demonstrate that rearing rats in isolation (i) produces a syndrome of generalized locomotor hyperactivity; (ii) increases the startle response; (iii) impairs prepulse inhibition; (iv) tends to increase food hoarding behavior; (v) increases basal dopamine turnover in the amygdaloid complex; (vi) decreases basal dopamine turnover in the infralimbic part of the medial prefrontal cortex; and (vii) decreases basal turnover of serotonin in the nucleus accumbens. In the entorhinal cortex, dopamine neurotransmission seemed to be more sensitive to the caging conditions since a decreased basal turnover of dopamine was observed in grid-reared animals. Plasma corticosterone levels were also increased in grid-reared animals compared with rats reared in sawdust cages. Finally, isolates reared on grids showed a significant positive correlation between plasma corticosterone levels and dopamine in the left nucleus accumbens.Altogether, these results support the contention that there is a link between social isolation, attention deficit, spontaneous locomotor hyperactivity and reduced dopamine turnover in the medial prefrontal cortex. Furthermore, our data demonstrate that rearing rats in grid-floor cages represents a form of chronic mild stress associated with increased corticosterone levels, decreased basal turnover of entorhinal dopamine and increased dopamine activity in the left nucleus accumbens. Finally, a significant and selective decrease in the basal turnover of serotonin in the nucleus accumbens of isolated rats may be linked to the isolation-induced locomotor hyperactivity.

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  • Chronic adolescent isolation in rodents (over 1 week or longer) has more profound effects, including hyper-reactivity to stress and increased aggression.

    “When rodent adolescent isolation occurs chronically, over 1 week or longer, it has even more profound effects. Chronically isolated adolescent rodents (isolated throughout the whole adolescent period) have shown abnormal behaviours such as hyper-reactivity to stressful situations45 and increased aggression.46”

    From The effects of social deprivation on adolescent development and mental health (2020) · cites this paper as [45]

  • Social isolation lowers prefrontal cortex dopamine, indicated by reduced turnover and reduced sensitivity to dopamine agonists.

    “Opposite to the effects on dopamine in the nucleus accumbens, PFC dopamine is decreased following social isolation, as evidenced by decreased turnover as well as decreased sensitivity to dopamine agonists (Baarendse et al., 2013; Heidbreder et al., 2000).”

    From The effects of early life stress on reward processing (2018) · cites this paper as Heidbreder et al., 2000

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Authors
Heidbreder, C. A., Weiss, I. C., Domeney, A. M., Pryce, C., Homberg, J., Hedou, G., Feldon, J., Moran, M. C., & Nelson, P.
Affiliations
ETH Zurich (CH)
Corresponding author
Heidbreder, C.A
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2000-10
Volume
100
Issue
4
Pages
749-768
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/s0306-4522(00)00336-5
OpenAlex
W2025385931
Cited by
404
References
94
Citations by year
2026: 4 · 2025: 12 · 2024: 10 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 19 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 18 · 2015: 23 · 2014: 16 · 2013: 24 · 2012: 17
FWCI
4.90
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
social isolation, early life stress, prepulse inhibition, acoustic startle response, food hoarding, locomotor hyperactivity, dopamine turnover, serotonin turnover, entorhinal cortex, nucleus accumbens, medial prefrontal cortex, amygdala, corticosterone, chronic mild stress, depression
MeSH terms
Acoustic Stimulation, Adrenocorticotropic Hormone, Animals, Behavior, Animal, Brain, Corticosterone, Dopamine, Endocrine System, Feeding Behavior, Functional Laterality, Male, Motor Activity, Serotonin, Social Isolation, Reflex, Startle, Syndrome, Microdialysis, Rats

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