Due to their role in modifying GPCR signaling, the expression of RGS proteins could be altered by chronic exposure to addictive drugs. Indeed, numerous studies have demonstrated that the expression levels of RGS genes and proteins in the brain are dynamically regulated with drugs of abuse [13]. Both elevations and reductions in RGS transcripts and protein have been described with exposure to addictive drugs, however, suggesting an important but poorly understood adaptive function with chronic drug exposure. We will consider two general classes of addictive drugs (see Box 1, [31]): psychostimulants, such as cocaine and methamphetamine, which lead to elevated dopamine (DA) levels and prolonged DA signaling; and morphine and the club drug GHB, which activate opioid and GABAB receptors, respectively. Acute administration of cocaine and amphetamines reduces RGS in some regions of the brain while increasing RGS in other regions (Table 1). Chronic exposure to psychostimulants generally increases levels of RGS transcripts. Acute administration of morphine typically increases RGS expression, while chronic exposure reduces RGS expression – the opposite response of psychostimulants. Exceptions to these general observations, however, may
