Quetiapine treatment corrects behavioral impairments and promotes neuroplasticity in a neurodevelopmental rat model of schizophrenia.

Since the 2000s, alterations in neuroplasticity within the prefrontal cortex (PFC) have been recognized as a core pathophysiological feature of schizophrenia. The neonatal ventral hippocampal lesion (nVHL) model in rats not only induces a wide range of behavioral alterations associated with symptoms of the disorder but also reproduces the neuroplasticity deficits observed in the PFC. Here, we tested whether the atypical antipsychotic quetiapine (QUET) attenuates behavioral and neuroplastic abnormalities in male rats with nVHL. Subchronic QUET treatment reduced hyperlocomotion in the open field test and improved recognition memory impairments assessed with the novel object recognition test (NORT). At the neuroplasticity level, QUET treatment partially reversed nVHL-induced deficits by restoring dendritic spine density and the proportion of mushroom spines in the basilar dendritic tree of PFC layer 3 pyramidal neurons, whereas PFC layer 5 neurons and nucleus accumbens spiny projection neurons remained unaffected. These findings provide new insights into the non-monoaminergic mechanisms underlying the clinical effects of atypical antipsychotics and may inform the development of novel pharmacotherapies.