Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

NEUROPHARMACOLOGY

卷:138

Article

Turner, Amy C.¹  Kraev, Igor¹  Stewart, Michael G.¹  Stramek, Agata¹  Overton, Paul G.²  Dommett, Eleanor J.^1,3 

[1] Open Univ, Sch Life Hlth & Chem Sci, Milton Keynes MK7 6AA, Bucks, England

[2] Univ Sheffield, Dept Psychol, Western Bank, Sheffield S10 2TN, S Yorkshire, England

[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychol, 2nd Floor Addison House, London SE1 1UL, England

关键词: Psychostimulants;    Attention deficit hyperactivity disorder;    Dendritic spines;    Synaptophysin;    Electrophysiology;   

DOI  :  10.1016/j.neuropharm.2018.05.033

来源: Elsevier

【 摘 要 】

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine. Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting amphetamine suppresses collicular output activity, counterbalancing the increased input. We also report, for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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