Questions and Answers
Which one of these is a long-lasting drug-induced change?
Changes in AMPA-R in the VTA
What is the common pathway for 'natural rewards' and addictive drugs?
Mesocorticolimbic DA pathway
What did the rats, given amphetamine repeatedly, show sensitization to?
Sucrose
What did the cycles of diets, weight loss, and overconsumption make the individuals?
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What allows Na in but not Ca?
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What did chronic exposure to drugs result in?
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Which brain area is important for stress responses, learning, and emotions?
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What is the common circuitry that mediates the effects of different drugs?
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What allows Ca in after the Mg block is removed?
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What did the animals who went through complete abstinence but had free access to food and sugar show?
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What did amphetamine cause in rats tested with sugar?
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What did the mesolimboc DA system mediate the effects of?
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What is the result of the accumulation of GluA1 subunits in the VTA neurons?
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What happens to the AMPA receptors after prolonged abstinence from drug self-administration?
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What is the consequence of chronic exposure to drugs on AMPA receptors in the NAc?
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What allows Ca to enter the post-synaptic cell regardless of depolarization after chronic drug exposure?
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What is the result of the recruitment of 'silent' AMPA receptors to the surface due to Ca2+ influx?
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What is the consequence of the replacement of GluA2-containing AMPA receptors with GluA2-lacking receptors after prolonged abstinence from drug self-administration?
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What is the impact of chronic exposure to drugs on the NMDA receptors in the NAc?
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Match the following neurotransmitter receptors with their function:
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Match the following cellular changes with their consequence:
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Match the following molecular changes with their impact:
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Chronic exposure to drugs results in a decrease in AMPA receptors on the membrane surface, leading to reduced excitation of the synapse.
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The replacement of GluA2-containing AMPA receptors with GluA2-lacking receptors after prolonged abstinence from drug self-administration leads to a highly excitable synapse.
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The accumulation of GluA1 subunits in the VTA neurons results in AMPA receptors constructed by these units only, which are highly permeable to Ca2+.
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Drugs elevate DA in the VTA through somato-dendritic release, stimulating D1 receptors on the terminals of glutamate neurons.
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Exposure to drugs can result in synaptic adaptations in the VTA that may last about 1 week.
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Study Notes
Drug-Induced Plasticity
- Some drug-induced changes are short-term, such as opening and closing ion channels, while others are long-lasting or even permanent.
Mesocorticolimbic Pathway
- All addictive drugs increase dopamine (DA) concentration in this pathway, which is also involved in "natural rewards".
- The mesolimbic DA system is a common pathway for both addictive drugs and natural rewards.
Cross-Sensitization
- Amphetamine and sucrose (sugar) show cross-sensitization in rats, meaning exposure to one substance increases the response to the other.
- Rats given amphetamine repeatedly showed sensitization to sucrose, taking more than rats given saline.
Dieting and Addiction
- Cycles of dieting and overeating can be harmful, leading to sensitization and increasing the response to addictive substances.
Mesocorticolimbic Pathway Interactions
- Many brain areas interact with the mesocorticolimbic pathway, which is important for stress responses, learning, and emotions.
Molecular Changes
- Chronic exposure to drugs results in long-term changes in AMPA receptors (AMPA-R) in the ventral tegmental area (VTA).
- AMPA-R has 4 subunits that allow Na+ ions in but not Ca2+ ions.
- NMDA receptors, on the other hand, have a Mg2+ block that can be popped out, allowing Ca2+ ions in.
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