For this technique, proteins are run across an immobile gel with a pH gradient until they stop at the point where their net charge is neutral. After separating by charge in one direction, sodium dodecyl sulfate is run in the other direction to separate the proteins by size. A two-dimensional map is created using this technique that can be used to match additional proteins later. One can usually match the function of a protein by identifying in an 2D PAGE in simple proteomics because many intracellular somatic pathways are known. In neuroproteomics, however, many proteins combine to give an end result that may be neurological disease or breakdown. It is necessary then to study each protein individually and find a correlation between the different proteins to determine the cause of a neurological disease. New techniques are being developed that can identify proteins once they are separated out using 2D PAGE. Protein Identification Protein separate techniques, such as 2D PAGE, are limited in that they cannot handle very high or low molecular weight protein species. Alternative methods have been developed to deal with such cases. These include liquid chromatography mass spectrometry along with sodium dodecyl sulfate polyacrylamide gel electrophoresis, or liquid chromatography mass spectrometry run in multiple dimensions. Compared to simple 2D page, liquid chromatography mass spectrometry can handle a larger range of protein species size, but it is limited in the amount of protein sample it handle at once. Liquid chromatography mass spectrometry is also limited in its lack of a reference map from which to work with. Complex algorithms are usually used to analyze the fringe results that occur after a procedure is run. The unknown portions of the protein species are usually not analyzed in favor of familiar proteomes, however. This fact reveals a fault with current technology; new techniques are needed to increase both the specificity and scope of proteome mapping. Applications Drug Addiction It is commonly known that drug addiction involves permanent synaptic plasticity of various neuronal circuits. Neuroproteomics is being applied to study the effect of drug addiction across the synapse. Research is being conducted by isolating distinct regions of the brain in which synaptic transmission takes place and defining the proteome for that particular region. Different stages of drug abuse must be studied, however, in order to map out the progression of protein changes along the course of the drug addiction. These stages include