Mandatoryfosb Experiment

associated vectors in the lab showed that over expression of ΔFosB in the nucleus accumbens alone was sufficient to produce this enhance sensitivity to cocaine reward, while over expression of ΔFosB in the dorsal striatum has not effect. Using Δjune antagonist we can provide the converse type of information. Δjun is an artificial protein with an N-terminus of jun cleaved. The N-terminus is the trans activation domaine on june proteins, meaning these mutant juns (Δjun proteins) can still dimerize to ΔFosB and form an AP-1 complex. The complex can still bind to AP-1 sites in response to genes, but the complex physiologically inactive, it cannot regulate transcription because jun is lacking its trans activation domaine. Marie Clair Pigman placed

Colleen McClung carried out a genome wide analysis of gene expression in nucleus accumbens using affirmative chips in mice treated with cocaine and also employing our bi-transgenic mouse model. Colleen came up with the following data. For a period of chronic administration of cocaine she was able to identity a set of genes regulated by cocaine and ask ourselves what fraction of those cocaine regulated genes were the effects mimicked by over expressions of ΔFosB or were those expressions blocked by ΔC-jun. This is how we now know that ΔFosB accounts for more than twenty-five precent of all genes regulated in the NAc. This leads us to suspect ΔFosB is important but by no means is it to one factor involved. Colleen also found that ΔFosB effects on gene transcription were quite complex that ΔFosB unregulated some genes but down regulated others. ΔFosB is a master protein that controls the levels of expression in many other genes by regulation of the actin cytoskeleton and induction and stabilization of dendritic

For example, a single drug exposure can produce a form of long term memory for brain cells by altering the strength in which cells communicate with one another, this is often referred to as long term potentiation (LTP). This event occurs through an excitatory receptor know as the AMPA receptor. These synaptic AMPA receptor are a family of distinct ionotropic glutamate-excitatory post-synaptic receptors widely expressed in the central nervous system, which are the primary memory receptors (AMPA receptor). Excitatory synapses contain AMPA-type receptors (AMPAR) to transmit signals and NMDA-type receptors (NMDAR) to trigger long-term changes in synaptic transmission: long-term potentiation (LTP) and long-term depression (LTD) [16]. It has been proven that an extremely short exposure to cocaine can change the ability for an NMDA receptor to express the different subunits. Cocaine changes the assembly of NMDA receptors, meaning the NMDA receptors are altered so much that calcium ions can not move through, the channel may not stay open and the ability of cocaine to produce plasticity. The NMDA receptor is important in understanding some of the mechanisms associated with the effect of drugs on the brain. Synaptic plasticity is the ability of neurons and their connections to change.