# Visualization of the existence of LEAP2 in the nucleus accumbens and its role in amphetamine-induced locomotor activity

## TL;DR

This study shows that LEAP2 in the nucleus accumbens can inhibit amphetamine-induced movement, but only under certain conditions.

## Contribution

The study reveals a state-dependent regulatory role of LEAP2 in amphetamine-induced locomotor activity.

## Key findings

- LEAP2 protein is present in the nucleus accumbens, mainly in neurons like medium spiny neurons.
- LEAP2 inhibits acute amphetamine-induced locomotor activity in a dose-dependent manner.
- Chronic amphetamine exposure eliminates the inhibitory effect of LEAP2.

## 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.

The online version contains supplementary material available at 10.1186/s13041-025-01227-5.