دانلود مقاله ISI انگلیسی شماره 69935
عنوان فارسی مقاله

اختلال مادام العمر نتایج عملکرد ناقل سروتونین در اختلال یادگیری ترس: واژگونی توسط محاصره گیرنده CRF1

کد مقاله سال انتشار مقاله انگلیسی ترجمه فارسی تعداد کلمات
69935 2015 11 صفحه PDF سفارش دهید محاسبه نشده
خرید مقاله
پس از پرداخت، فوراً می توانید مقاله را دانلود فرمایید.
عنوان انگلیسی
Lifelong disturbance of serotonin transporter functioning results in fear learning deficits: Reversal by blockade of CRF1 receptors
منبع

Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)

Journal : European Neuropsychopharmacology, Volume 25, Issue 10, October 2015, Pages 1733–1743

کلمات کلیدی
اضطراب؛ وحشت زدگی
پیش نمایش مقاله
پیش نمایش مقاله اختلال مادام العمر نتایج عملکرد ناقل سروتونین در اختلال یادگیری ترس: واژگونی توسط محاصره گیرنده CRF1

چکیده انگلیسی

The inability to associate aversive events with relevant cues (i.e. fear learning) may lead to maladaptive anxiety. To further study the role of the serotonin transporter (SERT) in fear learning, classical fear conditioning was studied in SERT knockout rats (SERT−/−) using fear potentiation of the startle reflex. Next, fear acquisition and concomitant development of contextual conditioned fear were monitored during training. To differentiate between developmental and direct effects of reduced SERT functioning, effects of acute and chronic SSRI treatment were studied in adult rats. Considering the known interactions between serotonin and corticotropin-releasing factor (CRF), we studied the effect of the CRFR1 antagonist CP154,526 on behavioral changes observed and determined CRF1 receptor levels in SERT−/− rats. SERT−/− showed blunted fear potentiation and enhanced contextual fear, which resulted from a deficit in fear acquisition. Paroxetine treatment did not affect acquisition or expression of fear-potentiated startle, suggesting that disturbed fear learning in SERT−/− results from developmental changes and not from reduced SERT functioning. Although CRF1 receptor levels did not differ significantly between genotypes, CP154,526 treatment normalized both cue- and contextual fear in SERT−/− during acquisition, but not expression of fear-potentiated startle. The disrupted fear acquisition and concomitant increase in contextual conditioned fear-potentiated startle fear in SERT−/− resembles the associative learning deficit seen in patients with panic disorder and suggests that normal SERT functioning is crucial for the development of an adequate fear neuro-circuitry. Moreover, the normalization of fear acquisition by CP154,526 suggests a role for central CRF signaling in the generalization of fear.

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