A single dose of the antipsychotic drug clozapine has long-term behavioral and functional effects in mice

A single dose of clozapine in mice induces decorrelation of dorsal cortical activity that persists up to 9 days, linked to specific layer 5 intratelencephalic neurons.

• Why it matters: Antipsychotic regimens aim for steady plasma levels, yet clinical benefits emerge over days to weeks; this mismatch raises the possibility that single-dose effects outlast receptor occupancy.
• What they did: Mice received one clozapine dose, and researchers tracked behavioral outcomes and cortical activity patterns for several days, identifying a layer 5 intratelencephalic neuron subset driving the effect.
• The result: The 9-day decorrelation coincided with increased reliability of long-range inhibitory functional influence, suggesting single-dose circuit changes may involve plasticity and motivate longer dosing intervals.

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