Abstract
Psychosocial stress can impact feeding behavior outcomes. Although many studies have examined alterations to food intake, little is known about how stress affects feeding behavior patterns. To determine the impact of psychological stress on feeding behavior patterns, mice were subjected to various psychosocial stressors (social isolation, intermittent high-fat-diet, or physical restraint) prior to timed observations in a feeding arena that incorporated multiple bait loci. In addition, in vivo microdialysis was used to assess the effects of stressors on the reward system by measuring dopamine levels in the nucleus accumbens (NAcc) shell. Impaired feeding behavior patterns characterized by significant deviations in bait selection (i.e. fixated feeding) and prolonged periods of eating (i.e. protracted feeding) were observed in stressed mice relative to non-stressed controls. In addition to clear behavioral effects, the stressors also negatively impacted dopamine levels at the nucleus accumbens shell. Normalization of dopamine reversed the fixated feeding behavior, whereas specifically inhibiting neuronal activity in the dopaminergic neurons of the ventral tegmental area that project to the nucleus accumbens shell caused similar impairments in feeding. Given that the deviations were not consistently accompanied by changes in the amount of bait consumed, body weight, or metabolic factors, the qualitative effects of psychosocial stressors on feeding behavior likely reflect perturbations to a critical pathway in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases.
Significance Statement Feeding behavior can be affected by neuropsychiatric disorders including psychosocial stressors, and the evaluation of eating behavior was mainly based on food intake. However, it is speculated that not only food intake but also feeding behavior patterns can be affected in such disorders. The biological processes underlying the feeding behavior patterns have not been clarified yet. We found that aberrant feeding behaviors in mice characterized by fixated feeding were provoked by psychosocial stressors. The qualitative effects of psychosocial stressors on feeding behavior reflect perturbations in the mesolimbic dopamine system. These findings provide compelling evidence that aberrations in feeding behavior patterns can be developed as sensitive biomarkers of psychosocial stress and possibly a prodromal state of neuropsychiatric diseases.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Conflict of interest statement: nothing to report
Abbreviations
- AAV
- Adeno-associated virus
- ASA
- ascorbic acid
- ASD
- autism spectrum disorders
- BAT
- brown adipose tissue
- CNO
- Clozapine N-oxide
- COVID-19
- coronavirus disease of 2019
- cp
- cerebral peduncle
- DA
- dopamine
- DAPI
- 4’,6-diamidino-2-phenylindole
- DAT
- Dopamine transporter
- DMSO
- Dimethyl sulfoxide
- DREADD
- Designer Receptors Exclusively Activated by Designer Drugs
- EDTA
- ethylenediaminetetraacetic acid
- FLEX
- flip-excision
- FTLD
- front temporal lobar degeneration
- HFD
- high-fat diet
- hM4Di
- human Gi-coupled M4 muscarinic receptor
- HPLC-ECD
- high performance liquid chromatography with electrochemical detector
- hSyn
- human synapsin
- IF
- interfascicular nucleus
- Int-HFD
- intermittent high fat diet
- IP
- interpeduncular nucleus
- mCherry
- Monomeric Cherry
- ml
- medial lemniscus
- NAcc
- Nucleus accumbens
- qPCR
- quantitative polymerase chain reaction
- SEM
- standard error of the mean
- SNCD
- substantia nigra, compact part, dorsal tier
- SNR
- substantia nigra, reticular part
- TH
- tyrosine hydroxylase transporter
- VTA
- ventral tegmental area
- WAT
- white adipose tissue