Devesh Mishra

Publications (2)8.18 Total impact

• Article: Ethanol Disrupts the Mechanisms of Induction of Long-Term Potentiation in the Mouse Nucleus Accumbens.

  Devesh Mishra, Xiaoqun Zhang, Karima Chergui
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  ABSTRACT: BACKGROUND: Long-term changes in the efficacy of glutamatergic synaptic transmission in reward-related brain regions such as the nucleus accumbens (NAc) are proposed to contribute to neuroadaptations that lead to drug addiction. Although alcohol is a widely used addictive substance, the cellular mechanisms by which it influences synaptic plasticity in the NAc are not elucidated. We therefore examined whether acute ethanol (EtOH) alters long-term potentiation (LTP) in the core region of the NAc and investigated the possible underlying mechanisms. METHODS: We measured field excitatory postsynaptic potential/population spike (fEPSP/PS) amplitude in mouse brain slices containing the NAc. We also used amperometry to detect, with carbon fiber electrode, evoked dopamine release in brain slices. RESULTS: In control slices, high-frequency stimulation (HFS) induced a stable LTP. LTP was reduced in slices perfused with EtOH (50 mM). Given that induction of LTP is dependent on glutamate acting on N-methyl-d-aspartate (NMDA) receptors and group I metabotropic glutamate receptors (mGluRs), we studied the ability of EtOH to modulate these 2 classes of receptors. NMDA (20 μM) depressed the amplitude of the fEPSP/PS, but this effect was not altered by EtOH in our experimental conditions. However, EtOH reversed the ability of the group I mGluR agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) (50 μM) to potentiate the depressant action of NMDA on the fEPSP/PS. We also examined whether EtOH could modulate dopamine release given that dopamine plays important roles in mediating the reinforcing actions of abused drugs and in the induction of LTP in the NAc. We found that EtOH reversibly decreased action potential-dependent dopamine release evoked by single stimulation pulses and by HFS trains in NAc slices. CONCLUSIONS: These results show that EtOH impairs the induction of LTP possibly through several mechanisms that include inhibition of group I mGluR-mediated potentiation of NMDA receptor function and of evoked dopamine release. This study provides additional support for a key role of glutamatergic and dopaminergic neurotransmission in the NAc in mediating the reinforcing effects of acute alcohol.
  Alcoholism Clinical and Experimental Research 05/2012; · 3.34 Impact Factor
• Article: Ethanol inhibits excitatory neurotransmission in the nucleus accumbens of adolescent mice through GABA(A) and GABA(B) receptors.

  Devesh Mishra, Karima Chergui
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  ABSTRACT: Age-related differences in various acute physiological and behavioral effects of alcohol have been demonstrated in humans and in other species. Adolescents are more sensitive to positive reinforcing properties of alcohol than adults, but the cellular mechanisms that underlie such a difference are not clearly established. We, therefore, assessed age differences in the ability of ethanol to modulate glutamatergic synaptic transmission in the mouse nucleus accumbens (NAc), a brain region importantly involved in reward mechanisms. We measured field excitatory postsynaptic potentials/population spikes (fEPSP/PS) in NAc slices from adolescent (22-30 days old) and adult (5-8 months old) male mice. We found that 50 mM ethanol applied in the perfusion solution inhibits glutamatergic neurotransmission in the NAc of adolescent, but not adult, mice. This effect is blocked by the gamma-aminobutyric acid (GABA)(A) receptor antagonist bicuculline and by the GABA(B) receptor antagonist CGP 55845. Furthermore, bicuculline applied alone produces a stronger increase in the fEPSP/PS amplitude in adult mice than in adolescent mice. Activation of GABA(A) receptors with muscimol produces a stronger and longer lasting depression of neurotransmission in adolescent mice as compared with adult mice. Activation of GABA(B) receptors with SKF 97541 also depresses neurotransmission more strongly in adolescent than in adult mice. These results demonstrate that an increased GABA receptor function associated with a reduced inhibitory tone underlies the depressant action of ethanol on glutamatergic neurotransmission in the NAc of adolescent mice.
  Addiction Biology 07/2011; · 4.83 Impact Factor