Drug Induced Plasticity Flashcards
Drug induced changes
cross sensitization between repeated exposure of amphetamine and sucrose. EXPERIMENT: animals repeatedly exposed to sucrose, given immediate sucrose. after a few weeks, they are challenged with an injection of amphetamine. show a sensitized response to amphetamine compared to control group. the main point is that cross sensitization between natural rewards and drug rewards are mediated by DA system. another adaptation is the reduced density of D2 receptors in the striatum (common effect for all substances people abuse). obesity - see this reduction in D2 receptor density.
molecular changes
chronic exposure to drug leads to changes in AMPA receptors in the VTA. drugs increase DA in the VTA which stimulates D1 receptors on the terminals of glutamate neurons. this increases the release of glutamate which acts on AMPA and NMDA receptors on VTA neurons. repeated exposure to drug results in more glutamate being released which acts on AMPA, slightly depolarizing the neuron, causing the Mg channel blocker on NMDA to pop off which allows an influx of Ca2+ into the neuron. Calcium in the cell causes the recruitment of more AMPA receptors on the membrane. the cell becomes even more responsive to glutamate since there are more AMPA receptors. due to this high activity, some of the AMPA receptors are different - ones that dont show the GluA2 subunit. The receptor lacking in this unit is now permeable to calcium. this leads to increased calcium levels in the cell. this increase in calcium impairs the function of the cell (toxic) so the cell changes morphologically. cell also increases production of tyrosine hydroxylase. TH levels in VTA increase while axons narrow so TH is not transported as efficiently to the terminals. TH levels lower than usual causes decreased DA release, affecting downstream pathways such as downregulation of receptors on post synaptic neurons.
