The Role of ABC Transporters in the Actions of Drugs of Abuse

Drugs of abuse are transport substrates for many ABC transporters and can also regulate their expression and function. Although this class of proteins has not been widely studied in addiction, ABC transporters are implicated in clinically significant actions of drugs of abuse, including primary subjective effects, side effects, and drug-drug interactions. It has been established that the ABC transporters predominantly expressed in blood-brain barrier have a considerable impact on the transport of drugs of abuse into the brain. These drugs of abuse include opioids, CNS-stimulants, cannabinoids, nicotine, and ethanol. This chapter will focus on summarizing the effects of alterations in the expression or activity of ABC transporter on behavioral responses to drugs of abuse that are relevant to addiction. This evidence establishes the potential importance of these genes in drug abuse and dependence. Additionally, this chapter will examine genetic evidence implicating variation in ABC transporter genes in the genetic basis for addiction. This evidence includes evidence from genome-wide association studies, and evidence suggesting the roles that this gene variance may play in the pharmacokinetic properties of drugs of abuse, including their CNS disposition, and consequently in the subjective outcomes of drug use that influence drug abuse, drug tolerance, and drug dependence. In addition, this chapter will consider manipulation of these transporters with co-administration of other drugs along with drugs of abuse that may impact their pharmacokinetic properties, abuse potential, and side effects.