Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. This dopamine hyperfunction is considered the result of an “endogenous sensitization” process, 1 1. The long-standing dopamine hypothesis of schizophrenia postulates that mesolimbic dopamine hyperfunction underlies the psychotic symptoms of the disorder. The finding that NAC disrupted LI incites a cautionary note and requires clarification. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Sensitization disrupted LI and amplified the locomotor response NAC disrupted LI in control mice. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed.

NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. Methods:ĭ-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks the dose was increased weekly from 1 to 3 mg/kg. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia.

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