Food anticipation, ghrelin, and anxiety in juvenile goldfish: evidence for a mesolimbic dopaminergic link?

Food anticipatory activity (FAA) is described as a circadian increase in locomotor activity preceding a predictable meal. In goldfish, FAA reflects an anxiety-like state associated with food expectation, which is not solely driven by circadian timing or passive metabolic signals related to prolonged fasting. This anxiogenic component is induced by ghrelin and reversed by ghrelin antagonism. Although ghrelin regulates FAA and engages dopaminergic reward circuits in mammals, the integration of ghrelin, dopamine, and anxiety within the context of FAA has not been established. Here, we investigated whether dopamine mediates ghrelin-induced anxiety during FAA in goldfish (Carassius auratus) using complementary behavioural, neurochemical, and transcriptional approaches. Pharmacological blockade of dopamine receptors during FAA revealed a prominent role of D2-like receptors in anxiety responses, although D1-like receptors are also involved. Consistently, ghrelin-induced anxiety-like behaviour was selectively reversed by D2 antagonism. Moreover, these D2-receptors were abundant in telencephalic regions associated with motivational processing. Furthermore, ghrelin increased dopamine and DOPAC levels in the telencephalic accumbens-like region and induced c-fos, tyrosine hydroxylase, and ghrelin receptor expression in the posterior tuberculum, a key dopaminergic nucleus in teleost equivalent to the ventral tegmental area (VTA). Together, these results demonstrate that ghrelin recruits a dopaminergic pathway to modulate anticipatory anxiety during FAA in goldfish, predominantly through D2-like receptors. Our findings support the existence of a ghrelin-dopamine pathway in teleost that is functionally analogous to the mammalian ghrelin-VTA-dopamine circuit, suggesting an evolutionarily conserved mechanism linking metabolic signals, reward processing, and affective states.