Neurotransmitter receptors play key roles in cellular communication and are targets for therapeutic intervention. However, development of tolerance to chronic drug treatment is one major reason for drug abuse. Previous studies indicate that drug tolerance is, in part, due to a loss of receptors resulting from a decrease of receptor MRNA. For example, steady-state MRNA levels for the GABA-A receptor complex are reduced. So far, little is known about the molecular mechanisms involved in the agonist-induced down-regulation of GABA-A receptor MRNA. Recently, several immortalized cell lines that express the GABA-A receptor subunit have been identified. These cell lines provide a preparation to investigate the underlying molecular mechanisms using molecular genetic and cellular biological approaches. Ongoing studies are aimed at identifying the factors which mediate the negative feedback by which agonist binding regulates receptor expression.
