Another comparative study analyzed gene expression in the extended amygdala (pooled samples of bed nucleus of the stria terminalis and central nucleus of the amygdala) of C57Bl/6J mice subjected to chronic exposure to four drugs of abuse (morphine, nicotine, Δ9-tetrahydrocannabinol and ethanol) or protracted abstinence (4 weeks) [36]. This study focused on a selection of hundred genes previously identified by genome-wide analysis as being regulated upon chronic activation of the mu opioid receptor. Principal component analysis revealed that the four drugs of abuse regulated distinct sets of genes immediately after treatment, but converged toward a common transcriptional signature following protracted abstinence. Clustering analysis identified one set of genes that were similarly down-regulated by all drugs 4 weeks into withdrawal. These nine genes were mapped to a network centered on the Htt gene and are known to be expressed in GABAergic medium spiny neurons.
