Abstract
Exposure to addictive drugs triggers synaptic plasticity in reward-related brain regions, such as the midbrain, nucleus accumbens and the prefrontal cortex. Effects of chronic drug exposure on other brain areas have not been fully investigated. Here, we characterize synaptic plasticity in motor cortex after methamphetamine self-administration in rats. We show that this causes a loss of corticostriatal plasticity in rat brain slices and impaired motor learning in the rotarod task. These findings are paralleled by the observation of a lack of transcranial magnetic stimulation-induced potentiation or depression of motor evoked potentials in human patients with addiction, along with poor performance in rotary pursuit task. Taken together, our results suggest that chronic methamphetamine use can affect behavioral performance via drug-evoked synaptic plasticity occluding physiological motor learning.
Highlights
IntroductionDrug-evoked synaptic plasticity has been proposed as a neural substrate of adaptive behavior.[1,2] Initial exposure to an addictive drug leads to insertion of calcium-permeable AMPA (α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and calcium-impermeable N-methyl-D-aspartate (NMDA) receptors in dopamine (DA) neurons of the ventral tegmental area;[3,4] chronic drug exposure alters synaptic transmission in medium spiny neurons of the nucleus accumbens synapses and, in some cases, at cortical synapses.[5,6]Most of these studies focused on drug-evoked synaptic plasticity in subcortical regions (for example, ventral striatum, amygdala, ventral tegmental area) and prefrontal cortex,[7,8] all of which receive projections from midbrain DA neurons
We found that these stimlation protocols failed to induce synaptic plasticity in METH SA group (Figures 1b–d) in both the motor cortex and DL striatum, whereas there was no difference in the dorsomedial striatum
We report that METH abuse can affect plasticity of the motor cortex in both drug-exposed rats and human addicts
Summary
Drug-evoked synaptic plasticity has been proposed as a neural substrate of adaptive behavior.[1,2] Initial exposure to an addictive drug leads to insertion of calcium-permeable AMPA (α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and calcium-impermeable N-methyl-D-aspartate (NMDA) receptors in dopamine (DA) neurons of the ventral tegmental area;[3,4] chronic drug exposure alters synaptic transmission in medium spiny neurons of the nucleus accumbens synapses and, in some cases, at cortical synapses.[5,6]Most of these studies focused on drug-evoked synaptic plasticity in subcortical regions (for example, ventral striatum, amygdala, ventral tegmental area) and prefrontal cortex,[7,8] all of which receive projections from midbrain DA neurons. Drug-evoked synaptic plasticity has been proposed as a neural substrate of adaptive behavior.[1,2] Initial exposure to an addictive drug leads to insertion of calcium-permeable AMPA (α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and calcium-impermeable N-methyl-D-aspartate (NMDA) receptors in dopamine (DA) neurons of the ventral tegmental area;[3,4] chronic drug exposure alters synaptic transmission in medium spiny neurons of the nucleus accumbens synapses and, in some cases, at cortical synapses.[5,6]. Drug abuse accompanies compulsive behavior and drug seeking that could result from altered motor-striatal plasticity and functioning
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