Ghrelin recruits specific subsets of dopamine and gaba neurons of different ventral tegmental area sub-nuclei

CORNEJO, MARÍA PAULA; BARRILE, FRANCO; DE FRANCESCO, PABLO NICOLÁS; PORTIANSKY, ENRIQUE LEO; REYNALDO, MIRTA; PERELLO, MARIO

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2018

0306-4522

Ghrelin is a stomach-derived hormone that regulates rewarding behaviors and reinforcement by acting on the ventral tegmental area (VTA). The VTA is a complex midbrain structure mainly comprised of dopamine (DA) and gamma-aminobutiric acid (GABA) neurons that are distributed in several VTA sub-nuclei. Here, we investigated the neuroanatomical distribution and chemical phenotype of ghrelin responsive neurons within the VTA. In wild-type mice, we found that: 1) ghrelin binding cells are present in most VTA sub-nuclei but not in its main target, the nucleus accumbens (Acb); 2) systemically-injected ghrelin increases food intake but does neither affect locomotor activity nor the levels of the marker of neuronal activation c-Fos in the VTA sub-nuclei; 3) centrally-injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; 4) intra-VTA-injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; 5) both centrally- and intra-VTA injected ghrelin increases c-Fos levels in DA neurons of the parabrachial pigmented VTA sub-nucleus. In genetically modified mice in which a subset of GABA neurons expresses the red fluorescent protein tdTomato, we found that centrally-injected ghrelin increases c-Fos levels in GABA neurons of the interfascicular VTA sub-nucleus. These results suggest that ghrelin can recruit specific subsets of VTA neurons in order to modulate food intake and locomotor activity.