The neonatal ventral hippocampal lesion as a heuristic neurodevelopmental model of schizophrenia

Traditionally, animal models of schizophrenia were predominantly pharmacological constructs focused on phenomena linked to dopamine and glutamate neurotransmitter systems, and were created by direct perturbations of these systems. A number of developmental models were subsequently generated that allowed testing of hypotheses about the origin of the disease, mimicked a wider array of clinical and neurobiological features of schizophrenia, and opened new avenues for developing novel treatment strategies. The most thoroughly characterized (∼100 primary research articles) is the neonatal ventral hippocampal lesion (NVHL) model, which is the subject of this review. We highlight its advantages and limitations, and how it may offer clues about the extent to which positive, negative, cognitive, and other aspects of schizophrenia, including addiction vulnerability, represent inter-related pathophysiological mechanisms.