Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive
Open accessAbstract
Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour.
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Two groups found a similar pattern in rodents: decreased willingness to work on progressive reinforcement but unchanged sucrose consumption when sucrose was given freely or on a fixed ratio.
“A similar pattern in rodents was identified by two groups, in which there was decreased willingness to work via progressive reinforcement but unchanged consumption of sucrose when it was given freely (Rüedi-Bettschen et al., 2005) or provided on a fixed ratio (Campbell et al., 2017).”
From The effects of early life stress on reward processing (2018) · cites this paper as Campbell et al., 2017
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The effects of early life stress on reward processing
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“, 2005) or provided on a fixed ratio (Campbell et al., 2017).”
Background
- Authors
- Campbell, E. J., Mitchell, C. S., Adams, C. D., Yeoh, J. W., Hodgson, D. M., Graham, B. A., & Dayas, C. V.
- Affiliations
- Hunter Medical Research Institute (AU)
- Corresponding author
- Dayas, Christopher V.
- ORCID
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2017-09-22
- Volume
- 46
- Issue
- 7
- Pages
- 2285-2296
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2752470269
- Cited by
- 17
- References
- 33
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2018: 4 · 2017: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Hunter Medical Research Institute
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- early life stress, lateral hypothalamus, motivated behavior, sucrose self-administration, chemogenetic activation, orexin, melanin-concentrating hormone, Fos expression, mood disorders, reward motivation
- MeSH terms
- Orexins, Animals, Female, Humans, Hypothalamus, Male, Motivation, Neurons, Receptors, Muscarinic, Recombinant Proteins, Stress, Psychological, Time, Designer Drugs, Oncogene Proteins v-fos, Rats, Wistar, Rats
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