Neural substrates and neuroendocrine mechanisms underlying neophobia in vertebrates

Neophobia, the avoidance of novel stimuli, is a widespread and ecologically relevant behavior observed across vertebrates and invertebrates. It is important for survival and adaptability, affecting how individuals navigate and use their environments. Neophobia might decrease an organism's exploitation of novel resources, but it also provides protection from potential dangers. Neophobia has been extensively studied in ecological and biomedical contexts, yet these two fields differ in their experimental paradigms, focal species and research goals. This Review uses a systematic approach to clarify the relationships between various 'neophobias' and the neural mechanisms that mediate them in vertebrates. Most vertebrate work focuses on mammals and, to a lesser extent, birds. In mammals and birds, both the hippocampus and amygdala (in birds, the medial ventral arcopallium) play a role in novelty evaluation and decision-making processes. In mammals, especially in the context of taste, food and odor neophobia, the insular and gustatory cortices also play a critical role. Serotonin, dopamine, glutamate, noradrenaline (norepinephrine) and glucocorticoids all exhibit context-, species- and life stage-dependent effects on neophobia. Fewer studies have examined immune or genetic mechanisms, and non-mammalian vertebrates are understudied relative to laboratory-bred rodents. In this Review, we also highlight persistent inconsistencies in how neophobia is defined and measured, emphasizing the need to distinguish it from neophilia and anxiety-related behaviors. Overall, this Review reveals both common mechanistic themes and major taxonomic and methodological gaps. We conclude by outlining key directions for future research, including broader comparative approaches and greater integration of ecological context into mechanistic studies of neophobia.