Abstract
BackgroundAll drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA). The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC). Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine.MethodsWe used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler) divergence analysis method for the present study.ResultsOur results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence) may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level.ConclusionsOur results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.
Highlights
All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA)
This significant enhancement induced by nicotine treatment (p < 0.01) is consistent with another previous report that 24 hours after a single, systemic administration of nicotine enhances the excitatory synapse strength on VTA DA neurons by enhancement of postsynaptic amino-3-hydroxy-5-methyl-4isoxazole propionic acid (AMPA) receptors [7]
To investigate whether prefrontal cortex (PFC) transection would cause the AMPA/NMDA peak ratio to be different, we repeated the same experiments in PFC transection rats
Summary
All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA). The dopamine (DA) neurons in the ventral tegmental area (VTA) and their projection areas, including prefrontal cortex (PFC), nucleus accumbens (NAc), and amygdala, are thought to be very important in the Malenka et al established a model to assess the glutamate receptor (GluR) plasticity and altered synaptic function by examining in vitro VTA DA neurons from midbrain slice preparation following 24 hours of a single, systemic administration of several types of drugs of addiction [6,7] Following administration, they found that the peak ratio of a-amino-3-hydroxy-5-methyl-4isoxazole propionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs) to N-methylD-aspartate (NMDA) receptor-mediated EPSCs was enhanced, which reflects a glutamatergic synapse plastic alteration onto DA neurons in the VTA. This may underlie a common mechanism of neural adaptation to addictive drugs [7]
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