Recurrent spaced concussions in adolescent rats disrupt cortical dopaminergic markers and induce behavioral hyperactivity and impaired object location memory.

Repeated concussions during critical stages of brain development can lead to lasting neural and behavioral changes. This study characterized the consequences of recurrent, spaced concussions using a clinically relevant adolescent Wistar rat model. Male rats were subjected to ten spaced concussions via a weight-drop model during adolescence (P42-P73) and subsequently underwent neurobehavioral, neurochemical, and histological analysis. Behaviorally, the concussion protocol induced hyperactivity in the open-field test and produced specific deficits in the Novel Object Location task; in contrast, performance was unimpaired in the Novel Object Recognition and Barnes Maze tests. These behavioral outcomes were accompanied by disruptions to cortical dopaminergic and GABAergic systems, including reduced dopamine D2 receptor levels, lower monoamine oxidase-A activity, and decreased brain-derived neurotrophic factor (BDNF) and increased gamma-aminobutyric acid decarboxylase 67 (GAD67) expression. Concurrently, glial fibrillary acidic protein (GFAP) expressions were elevated in specific corticolimbic regions. Importantly, these alterations occurred without severe injury markers, such as loss of consciousness or albumin extravasation. Our findings demonstrate that spaced concussive events during adolescence are sufficient to produce distinct behavioral and neurochemical deficits. This work highlights dopaminergic dysfunction as a key etiological factor and potential therapeutic target for impairments following repeated concussions in the developing brain.