Ghrelin receptor agonist MK0677 and overnight fasting do not rescue deficient fear extinction in 129S1/SvImJ mice.

Fritz EM, Pierre A, De Bundel D, Singewald N

Frontiers in psychiatry9 Feb 2023Cited by 1 (Europe PMC)

PMID36846243PMCIDPMC9947350DOI10.3389/fpsyt.2023.1094948PepBankPUB-36846243

Summary

The hunger hormone ghrelin has been implicated in the modulation of anxiety- and fear-related behaviors in rodents and humans, while its dysregulation may be associated with psychiatric illness. Along these lines, the ghrelin system has been suggested as a potential target to facilitate fear extinction, which is the main mechanism underlying cognitive behavioral therapy. So far, this hypothesis has not been tested in individuals that have difficulties to extinguish fear. Thus, we investigated pharmacological (ghrelin receptor agonist MK0677) and non-pharmacological (overnight fasting) strategies to target the ghrelin system in the 129S1/SvImJ (S1) mouse strain, which models the endophenotype of impaired fear extinction that has been associated with treatment resistance in anxiety and PTSD patients. MK0677 induced food intake and overnight fasting increased plasma ghrelin levels in S1 mice, suggesting that the ghrelin system is responsive in the S1 strain. However, neither systemic administration of MK0677 nor overnight fasting had an effect on fear extinction in S1 mice. Similarly, our groups previously reported that both interventions did not attenuate fear in extinction-competent C57BL/6J mice. In summary, our findings are in contrast to several studies reporting beneficial effects of GHSR agonism and overnight fasting on fear- and anxiety-related behaviors in rodents. Rather, our data agree with accumulating evidence of divergent behavioral effects of ghrelin system activation and underscore the hypothesis that potential benefits of targeting the ghrelin system in fear extinction may be dependent on factors (e.g., previous stress exposure) that are not yet fully understood.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
MK0677 induced food intake in 129S1/SvImJ mice.
In plain wordsIn mice of the 129S1/SvImJ strain, MK0677 stimulated food intake.
Peptide
MK-677 (ibutamoren)
Outcome
IncreaseFood intake
Study
micen: not reported in source
129S1/SvImJ mice
Outcome group
Appetite and food intake · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
MK0677 induced food intake and overnight fasting increased plasma ghrelin levels in S1 mice, suggesting that the ghrelin system is responsive in the S1 strain.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we investigated pharmacological (ghrelin receptor agonist MK0677) and non-pharmacological (overnight fasting) strategies to target the ghrelin system in the 129S1/SvImJ (S1) mouse strain, which models the endophenotype of impaired fear extinction that has been associated with treatment resistance in anxiety and PTSD patients.
Show in the study text Report a problemFND-3684624301
02AnimalAnimal study (in vivo)Efficacy outcome
Systemic MK0677 administration did not affect fear extinction in 129S1/SvImJ mice.
In plain wordsIn mice of the 129S1/SvImJ strain, systemic MK0677 did not improve fear extinction.
Peptide
MK-677 (ibutamoren)
Outcome
No significant changeFear extinction
Study
micen: not reported in source
129S1/SvImJ mice
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
Dose not stated · systemicAs given in this study (mice).
Source sentences
Summary
However, neither systemic administration of MK0677 nor overnight fasting had an effect on fear extinction in S1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Thus, we investigated pharmacological (ghrelin receptor agonist MK0677) and non-pharmacological (overnight fasting) strategies to target the ghrelin system in the 129S1/SvImJ (S1) mouse strain, which models the endophenotype of impaired fear extinction that has been associated with treatment resistance in anxiety and PTSD patients.
Show in the study text Report a problemFND-3684624302

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Version history

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Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

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