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2011 | 71 | S |
Tytuł artykułu

D-cycloserine and midazolam change the expression ALPHA-2 subunits of GABA-A receptor and gephyrin in the limbic structures as well as GABA release of high and low anxiety rats

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
We examined the effects of midazolam and D-cycloserine on the release of GABA in the basolateral amygdala (BLA) of high (HR) and low (LR) anxiety rats during extinction session of a conditioned fear test. HR and LR anxiety rats were selected according to their behaviour in the contextual fear test (i.e., the duration of a freezing response was used as a discriminating variable). Administration of D-cycloserine (15 mg/kg, i.p.), significantly enhanced the inhibition of an aversive context-induced freezing response observed during the extinction session in HR and LR rats 7 days after contextual fear test. It was also found that midazolam and D-cycloserine facilitated the GABA release in HR rats under the influence of conditioned fear. HR rats pretreated with saline had higher expression of alpha-2 subunits of GABA-A receptor in BLA compared to LR rats. Administration of D-cycloserine and midazolam increased the expression of alpha-2 subunits in the BLA of HR rats compared to HR rats pretreated with saline, and to drug administered LR rats. Moreover, D-cycloserine enhanced the expression of alpha-2 subunits and gephyrin in the prefrontal cortex of HR rats. Together, these findings suggest that animals that are more vulnerable to stress differ in the expression of alpha-2 subunits of GABA-A receptor in amygdala and prefrontal cortex which is involved in the control of emotional behaviour. These animals might have innate deficits in forebrain systems that control the activity of the limbic structures including GABAergic innervation of the BLA. These data indicate also possible neurochemical mechanisms for individual differences observed in response to anxiolytic drugs among patients with anxiety disorders. The current results also suggest that activation of glutamatergic function can initiate neural changes which improve fear extinction and provide preclinical evidence in support of the clinical use of NMDA(R) modulators for the treatment of anxiety-related disorders.
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Wydawca
-
Rocznik
Tom
71
Numer
S
Opis fizyczny
p.90
Twórcy
autor
  • Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland
  • Department of Experimental and Clinical Pharmacology, Medical University, Warsaw, Poland
  • Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland
autor
  • Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland
  • Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland
autor
  • Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland
  • Department of Experimental and Clinical Pharmacology, Medical University, Warsaw, Poland
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Typ dokumentu
Bibliografia
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bwmeta1.element.agro-02f0f8f9-02c9-4ce7-b553-3a3d51b0f6bb
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