Chronic Ethanol and Withdrawal Differentially Modulate Pre- and Post-synaptic Function at Glutamatergic Synapses in Rat Basolateral Amygdala Abbreviated Title: Ethanol and withdrawal alter BLA glutamatergic transmission
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چکیده
Withdrawal anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is long lasting, can manifest well after the overt physical symptoms of withdrawal, and is frequently associated with relapse in recovering alcoholics. The neurobiological mechanisms governing these withdrawal-associated increases in anxiety are currently unknown. The basolateral amygdala is a major emotional center in the brain and regulates the expression of both learned-fear and anxiety. Neurotransmitter system alterations within this brain region may therefore contribute to withdrawal-associated anxiety. Since evidence suggests that glutamate-gated neurotransmitter receptors are sensitive to acute ethanol exposure, we examined the effect of chronic intermittent ethanol (CIE) and withdrawal (WD) on glutamatergic synaptic transmission in the basolateral amygdala. We found that slices prepared from CIE and WD animals had significantly increased contributions by synaptic NMDA-receptors. In addition, CIE increased the amplitude of AMPA receptormediated spontaneous excitatory postsynaptic currents (sEPSC), while only WD altered the amplitude and kinetics of tetrodotoxin-resistant spontaneous events (mEPSC). Similarly, the frequency of sEPSCs was increased in both CIE and WD neurons; but, only WD increased the frequency of mEPSCs. These data suggest that CIE and WD differentially alter both preand post-synaptic properties of BLA glutamatergic synapses. Finally, we show that microinjection of the AMPA receptor antagonist, DNQX, can attenuate withdrawal-related anxiety-like behavior. Together, our results suggest that increased glutamatergic Page 2 of 54
منابع مشابه
Chronic ethanol and withdrawal differentially modulate pre- and postsynaptic function at glutamatergic synapses in rat basolateral amygdala.
Withdrawal anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is long-lasting, can manifest well after the overt physical symptoms of withdrawal, and is frequently associated with relapse in recovering alcoholics. The neurobiological mechanisms governing these withdrawal-associated increases in anxiety are currently unknown. The basolateral amygd...
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Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates...
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Chronic exposure to alcohol produces adaptations within the basolateral amygdala (BLA) that are associated with the development of anxiety-like behaviors during withdrawal. In part, these adaptations are mediated by plasticity in glutamatergic synapses occurring through an AMPA receptor mediated form of post-synaptic facilitation in addition to a unique form of presynaptic facilitation. In comp...
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