Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders
Abstract
:1. Introduction
2. The NPS/NPSR1 System and Stress-Relevant Endpoints in Rodents
2.1. Role of the NPS/NPSR1 System in Anxiety- and Fear-Related Behaviours
2.2. Role of the NPS/NPSR1 System in Social Behaviours and Aggression
2.3. Role of the NPS/NPSR1 System in Stress Responsiveness and Stress-Coping Behaviour
2.4. Role of the NPS/NPSR1 System in Animal Models of Psychiatric Disorders
2.4.1. The NPS/NPSR1 System and Pathological Anxiety and Fear
2.4.2. The NPS/NPSR1 System and the Exposure to Acute Stressors
Drug | Site | Test | Behaviour | Findings | Ref. |
---|---|---|---|---|---|
NPS | i.c.v. | EP/ZM, DaLi, MBT, DBT | Anxiety | ↓ ♂/♀ | [1,21,22,23,24,25,26,27,28,29,31] |
EPM, ETM | ↔ | [32,33,34] | |||
LA, BLA | EPM | ↔ | [51,58] | ||
LA/BLA | EPM, DaLi | ↓ | [41] | ||
MeA, VMH, PVN | EPM | ↓ | [21,40,43] | ||
VH | EPM | ↓ | [44] | ||
DaLi | ↔ | ||||
intranasal | EPM | ↓ | [23,53] | ||
NPSR1-A | i.p. (SHA68) | EPM | Anxiety | ↔ | [43] |
Anxiolytic effects of intra-VMH NPS | X | ||||
NPS | i.c.v. | FST, TST | Stress-coping | ↔ ♂/♀ | [22,28] |
NPS | i.c.v. | SPAT | Sociability | ↔ | [23,34,48] |
Social recognition | ↔ | [23] | |||
RI | Aggression | ↓ ↔ | [48,49] | ||
intranasal | SPAT | Sociability | ↔ | [23] | |
NPSR1-A | i.c.v. ((d-Cys(tBu)5)NPS) | SPAT | Sociability | ↔ | [23] |
i.p. (SHA68) | RI | Anti-aggressive effects of i.c.v. NPS | Ø | [49] | |
i.c.v. ((tBu-D-Gly5)NPS) | Anti-aggressive effects of i.c.v. NPS | X | |||
NPS | i.c.v. | CuFC | EXT | ↑ | [34] |
EXT recall | ↔ | ||||
LA | CuFC | EXP, EXT | ↔ | [58] | |
Contextual fear renewal | ↔ | ||||
BLA | ASR | Magnitude | ↔ | [51] | |
trauma cue | Freezing | ↔ | [51] | ||
LA/BLA | CuFC | EXP | ↔ | [41] | |
EXT | ↑ | ||||
Contextual fear renewal | ↓ | ||||
EXT recall | ↔ | ||||
NPSR1-A | i.c.v. ((d-Cys(tBu)5)NPS) | SFC | EXP | ↔ | [34] |
LA (SHA68) | CuFC | EXP, EXT | ↔ | [58] | |
Contextual fear renewal | ↔ | ||||
LA/BLA (SHA68) | CuFC | EXT | ↓ | [41] | |
Contextual fear renewal | ↑ |
Strain Background | Sex | Test | Behaviour | Findings | Ref. |
---|---|---|---|---|---|
C57/BL6J mice | ♂/♀ | EPM, DaLi, MBT | Anxiety | ↔ | [30,36,37,38] |
FST | Passive stress-coping | ↑ ♂ | [30] | ||
TST | ↔ | ||||
SPAT | Sociability | ↔ | [39] | ||
Social novelty | ↔ | ||||
SFC | EXP | ↔ | [39] | ||
EXT | ↑ | ||||
CFC | EXP | ↔ | [37] | ||
Context discrimination | ↔ | [37,38] | |||
↑ | [37] | ||||
CuFC | EXP, EXT | ↔ | [36] | ||
Safety learning | Freezing | ↔ | [38] | ||
ASR | Magnitude, Vmax | ↔ | [38,41] | ||
↓♂ | [30,36] | ||||
- | Basal CORT | ↔ | [37,38] | ||
Stress-induced CORT | ↔ | [30,38] | |||
Locomotion | Cocaine-induced | ↔ | [36] | ||
CD1 mice | ♂ | EPM, ETM | Anxiety | ↔ | [26,33] |
FST | Stress-coping | ↔ | [26] | ||
RI | Aggression | ↑ | [49] | ||
SIH | Stress response | ↔ | [36] |
3. Role of the NPS/NPSR1 System in Addiction-Like Behaviours
3.1. Role of the NPS/NPSR1 System in Drug-Induced Conditioned Place Preference
3.2. Role of the NPS/NPSR1 System in Drug Self-Administration
3.2.1. The NPS/NPSR1 System and Operant Self-Administration
3.2.2. The NPS/NPSR1 System and Oral Self-Administration
3.3. Role of the NPS/NPSR1 System in Drug Intoxication and Withdrawal
Drug | Site | Test | Drug of Abuse | Behaviour | Findings | Ref. |
---|---|---|---|---|---|---|
NPS | i.c.v. | CPP | Cocaine | EXP, EXT | ↔ | [62] |
RST | ↑ | |||||
Morphine | EXP | ↓ | [61] | |||
NPS | EXP | ↔ | [61,65] | |||
↑ | [64] | |||||
NPSR1-A | i.p. (SHA68) | CPP | Cocaine | RST | ↔ | [62] |
RST (stress) | X | |||||
RST (i.c.v. NPS) | X | |||||
NPS | i.c.v. | oral | Ethanol | Intake | ↓ | [65] |
Anxiety | ↓ | |||||
Stress-coping | ↓ | |||||
BLA | Anxiety | ↓ | ||||
i.c.v. | IG | Ethanol | Anxiety (WD) | ↓ | [73] | |
s.c. | Morphine | Anxiety (WD) | ↓ | [74] | ||
NPS | i.c.v., LH, PeF | SA | Cocaine | SA (FR) | ↔ | [66] |
RST (cue) | ↑ | [24,66] | ||||
DMH, CeA | RST (cue) | ↔ | [66] | |||
i.c.v. | SA | Ethanol | SA (FR) | ↔ | [32,70] | |
RST (cue, NPS) | ↑ | |||||
TBC | Intake | ↔ ♀ | [71] | |||
LH | SA | RST (cue) | ↑ | [70] | ||
NPS | i.c.v., LH, PVN | - | Palatable food | Intake | ↓ | [69] |
CeA | Intake | ↔ | ||||
i.c.v. | SA | NPS | SA (FR) | ↑ | [64] | |
NPSR1-A | i.p. (SHA68) | SA | Cocaine | SA (FR) | ↔ | [66] |
↓ | [68] | |||||
RST (cue) | ↓ | [66] | ||||
i.p. (NPSR1-QA1) | SA (FR) | ↔ | [67] | |||
RST (cue) | ↓ | |||||
i.p. (RTI-118) | SA (FR) | ↓ | [68] | |||
RST (cue, stress, cocaine) | ↓ | |||||
i.c.v., CeA ((d-Cys(tBu)5)NPS) | RST (cue) | ↔ | [67] | |||
LH, PeF ((d-Cys(tBu)5)NPS) | RST (cue) | ↓ | [66,67] | |||
i.p. (NCGC84) | Ethanol | SA (FR, PR) | ↓ | [72] | ||
Motivation | ↓ | |||||
RST (cue) | ↔ | |||||
i.c.v. ((d-Cys(tBu)5)NPS) | - | Palatable food | Intake | ↔ | [69] | |
Anorectic effects of i.c.v. NPS | X |
4. Alterations in the NPS/NPSR1 System in Stress-Related Disorders
4.1. Role of the NPS/NPSR1 System in Affective Disorders
4.2. Role of the NPS/NPSR1 System in Substance Use Disorders
4.3. Role of the NPS/NPSR1 System in Anxiety Symptom Severity
5. Role of the NPS/NPSR1 System in Emotion Regulation and Stress Responses in Healthy Individuals
5.1. SNP rs324981, Anxiety Sensitivity and Fear Rating
5.2. SNP rs324981, Coping Abilities and Experiences of Life Stress
5.3. SNP rs324981 and Neuroendocrine Stress Responsiveness
Parameter | TT | AT | AA | Ref. | |
---|---|---|---|---|---|
Emotional symptoms | |||||
Anxiety sensitivity (emotional task) | ↔ | ↔ | ↔//↑ | [88]//[95,96,97,98] | |
Anxiety sensitivity (attentional task) | ↔ | ↔ | ↔ | [99] | |
Anxiety sensitivity (experience of life stress) | ↑ | ↔ | ↔ | [101] | |
Panic agoraphobia | ↔ | ↔ | ↔ | [96] | |
Baseline panic symptoms | ↑ | ↔ | ↔ | [100] | |
CCK-4-induced panic symptoms | ↔ | ↔ | ↔ | [100] | |
Depression symptoms | ↔ | ↔ | ↔ | [95,96] | |
Fear rating (fear conditioning) | ↑ | ↑ | ↔ | [89] | |
Startle magnitude to positive stimuli | ↔ | ↔ | ↔ | [90] | |
Startle magnitude to negative stimuli | ↓//↑$ | ↓//↑$ | ↔ | [88]//[90] | |
Startle magnitude to neutral stimuli | ↑ | ↑ | ↔ | [88,90] | |
Coping abilities and personality traits | |||||
Trait anxiety if low self-efficacy | ↑ | ↑ | ↑ | [102] | |
Trait anxiety if high self-efficacy | ↑ | ↓ | ↓ | ||
Adaptive impulsivity | ↓ | ↔ | ↑ | [103] | |
Adaptive impulsivity (experience of life stress) | ↑ | ↔ | ↓ | ||
Maladaptive impulsivity (experience of life stress) | ↑ | ↔ | ↑ | ||
Hyperactivity | ↑ | ↔ | ↔ | ||
Hyperactivity (experience of life stress) | ↑ | ↔ | ↔ | ||
Openness to experiences | ↓ | ↔ | ↑ | ||
Neuroticism (experience of life stress) | ↔ | ↔ | ↑ | ||
Extraversion (experience of life stress) | ↔ | ↔ | ↓ | ||
Stress responses | |||||
Baseline CORT | ↔ | ↔ | ↔ | [104,105] | |
↑ CORT (stress or CCK-4 challenge) | ↔//↑♂ | ↔ | ↔ | [100]//[104,105,106] | |
↑ ACTH (stress or CCK-4 challenge) | ↔ | ↔ | ↔ | [106] | |
↑ Heart rate (stress or CCK-4 challenge) | ↔ | ↔ | ↔ | [100,106] | |
Skin conductance level (emotional task) | ↔ | ↔ | ↔ | [89,97] | |
Subjective stress rating (TSST) | ↔ | ↔ | ↔ | [105] |
5.4. Neurobiological Mechanisms in Healthy Individuals
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Brain Area | TT | AT | AA | Ref. |
---|---|---|---|---|
Neural activation to stress or CCK-4 challenge | ||||
Parahippocampal gyrus | ↑♂, ↓♀ | ↔ | ↔ | [104] |
Amygdala | ↔ | ↔ | ↔ | [104,105] |
Anterior cingulate cortex | ↔ | ↔ | ↔//↑ | [100]//[104,106] |
Cerebellum | ↑ | ↔ | ↔ | [106] |
Neural activation in an emotional task | ||||
Dorsolateral prefrontal cortex | ||||
Positive stimuli | ↓ | ↓ | ↔ | [96,97] |
Negative stimuli | ↑ | ↑ | ↑ | |
Neutral stimuli | ↔ | ↔ | ↔ | |
Medial prefrontal cortex | ||||
Positive stimuli | ↓ | ↓ | ↔ | [96,97] |
Negative stimuli | ↑ | ↑ | ↑ | |
Neutral stimuli | ↔ | ↔ | ↔ | |
Rostro dorsal anterior cingulate cortex/Dorsomedial prefrontal cortex | ↑ | ↑ | ↔ | [89] |
Amygdala | ↑ | ↑ | ↔ | [95] |
Neural activation in a cognitive task | ||||
Dorsolateral prefrontal cortex | ↔ | ↔ | ↑ | [96] |
Medial prefrontal cortex | ↔ | ↔ | ↔ | |
Neural activation in an attentional task | ||||
Superior parietal lobule | ↑ | ↔ | ↔ | [99] |
(Dorsolateral) Prefrontal cortex | ↑ | ↔ | ↔ | |
Locus coeruleus | ↑ | ↔ | ↔ |
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Tobinski, A.-M.; Rappeneau, V. Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders. Pharmaceuticals 2021, 14, 780. https://doi.org/10.3390/ph14080780
Tobinski A-M, Rappeneau V. Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders. Pharmaceuticals. 2021; 14(8):780. https://doi.org/10.3390/ph14080780
Chicago/Turabian StyleTobinski, Ann-Marie, and Virginie Rappeneau. 2021. "Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders" Pharmaceuticals 14, no. 8: 780. https://doi.org/10.3390/ph14080780