Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity
Abstract The nucleus accumbens (NAcc) is a key brain region in reward circuitry, mediating responses to psychostimulants, such as amphetamine (AMPH), including locomotor activity. This effect is known to be enhanced by the orexigenic neuropeptide ghrelin acting through growth hormone-secretagogue re...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13041-025-01227-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849767102384177152 |
|---|---|
| author | Seohyeon Lee Ga Young Yoo Hyung Shin Yoon Jeong-Hoon Kim |
| author_facet | Seohyeon Lee Ga Young Yoo Hyung Shin Yoon Jeong-Hoon Kim |
| author_sort | Seohyeon Lee |
| collection | DOAJ |
| description | Abstract The nucleus accumbens (NAcc) is a key brain region in reward circuitry, mediating responses to psychostimulants, such as amphetamine (AMPH), including locomotor activity. This effect is known to be enhanced by the orexigenic neuropeptide ghrelin acting through growth hormone-secretagogue receptors (GHSR) expressed in the region. Recently, liver-expressed antimicrobial peptide 2 (LEAP2) was identified as another ligand for GHSR that opposes ghrelin’s action. Based on its antagonism, we hypothesized that LEAP2 modulates AMPH-induced locomotor activity in the NAcc. To examine this, we first confirmed the presence of LEAP2 protein in this NAcc and observed that its fluorescent signals were predominantly localized in neurons, including medium spiny neurons (MSNs). We then investigated whether LEAP2 microinjection alters AMPH-induced locomotor activity. Our findings showed that LEAP2 inhibited acute AMPH-induced locomotor activity in a dose-dependent manner. However, its inhibitory effects were absent following chronic AMPH exposure, indicating that the effect of LEAP2 on AMPH-induced locomotor activity varies depending on drug-exposed physiological status. These results provide new insights into a state-dependent regulatory role of LEAP2 in AMPH-induced locomotor activity. |
| format | Article |
| id | doaj-art-fa352c5df15e45f890a31e886414acfc |
| institution | DOAJ |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj-art-fa352c5df15e45f890a31e886414acfc2025-08-20T03:04:21ZengBMCMolecular Brain1756-66062025-07-011811910.1186/s13041-025-01227-5Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activitySeohyeon Lee0Ga Young Yoo1Hyung Shin Yoon2Jeong-Hoon Kim3Department of Medical Sciences, Yonsei University College of MedicineDepartment of Medical Sciences, Yonsei University College of MedicineDepartment of Physiology, Yonsei University College of MedicineDepartment of Medical Sciences, Yonsei University College of MedicineAbstract The nucleus accumbens (NAcc) is a key brain region in reward circuitry, mediating responses to psychostimulants, such as amphetamine (AMPH), including locomotor activity. This effect is known to be enhanced by the orexigenic neuropeptide ghrelin acting through growth hormone-secretagogue receptors (GHSR) expressed in the region. Recently, liver-expressed antimicrobial peptide 2 (LEAP2) was identified as another ligand for GHSR that opposes ghrelin’s action. Based on its antagonism, we hypothesized that LEAP2 modulates AMPH-induced locomotor activity in the NAcc. To examine this, we first confirmed the presence of LEAP2 protein in this NAcc and observed that its fluorescent signals were predominantly localized in neurons, including medium spiny neurons (MSNs). We then investigated whether LEAP2 microinjection alters AMPH-induced locomotor activity. Our findings showed that LEAP2 inhibited acute AMPH-induced locomotor activity in a dose-dependent manner. However, its inhibitory effects were absent following chronic AMPH exposure, indicating that the effect of LEAP2 on AMPH-induced locomotor activity varies depending on drug-exposed physiological status. These results provide new insights into a state-dependent regulatory role of LEAP2 in AMPH-induced locomotor activity.https://doi.org/10.1186/s13041-025-01227-5LEAP2Nucleus accumbensAmphetamineNeuropeptideLocomotor activity |
| spellingShingle | Seohyeon Lee Ga Young Yoo Hyung Shin Yoon Jeong-Hoon Kim Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity Molecular Brain LEAP2 Nucleus accumbens Amphetamine Neuropeptide Locomotor activity |
| title | Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity |
| title_full | Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity |
| title_fullStr | Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity |
| title_full_unstemmed | Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity |
| title_short | Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity |
| title_sort | visualization of the existence of leap2 in the nucleus accumbens and its role in amphetamine induced locomotor activity |
| topic | LEAP2 Nucleus accumbens Amphetamine Neuropeptide Locomotor activity |
| url | https://doi.org/10.1186/s13041-025-01227-5 |
| work_keys_str_mv | AT seohyeonlee visualizationoftheexistenceofleap2inthenucleusaccumbensanditsroleinamphetamineinducedlocomotoractivity AT gayoungyoo visualizationoftheexistenceofleap2inthenucleusaccumbensanditsroleinamphetamineinducedlocomotoractivity AT hyungshinyoon visualizationoftheexistenceofleap2inthenucleusaccumbensanditsroleinamphetamineinducedlocomotoractivity AT jeonghoonkim visualizationoftheexistenceofleap2inthenucleusaccumbensanditsroleinamphetamineinducedlocomotoractivity |