Transcripts encoding calcium/calmodulin-related signaling transcripts were decreased, which was validated for CALM2 by QPCR ( Fig. 3 ). Studies in human postmortem brain have previously demonstrated a general decrease in calcium/cAMP-related signaling transcripts in frontal and motor cortex of human alcoholics [13], a decrease in adenylate cyclase (AC) type I (AC-I) protein levels and activity in temporal and frontal cortex in alcoholics [22]–[23] and in AC-I mRNA and protein in temporal cortex from heroin addicts [24]. While AC-I protein levels were unchanged in prefrontal cortex from opiate addicts, there were significant decreases in the downstream MAPK signaling cascade [25]. Furthermore, methamphetamine administration decreased calcium/calmodulin-dependent protein kinase II (CAMKII) activity and phosphorylated (but not total) CAMKIIα in rat frontal and parietal cortex [26].