Laboratory studies indicate that cocaine's effects on the dopaminergic function are due to its primary action of blocking the reuptake of dopamine from the synaptic cleft, an action of cocaine directed at the specific dopamine transporter. It has also been determined that cocaine similarly blocks the reuptake of serotonin and norepinephrine. Recent laboratory studies, however, show that chronic cocaine administration profoundly disrupts the endogenous opioid system. Extensive studies have been conducted using an animal model based on the "binge" pattern of cocaine administration. Findings from these studies demonstrate the significant disruption of both dynorphin gene expression and kappa opioid receptor gene expression in the chronic cocaine administration setting. The findings may have significance for the development of new pharmacotherapeutic agents that may be directed to specific components of the endogenous opioid system and possibly to the kappa opioid receptor system. Additional studies have been initiated to further examine the role of the dynorphin peptide-kappa opioid receptor system in the normal physiological functioning of humans. 84 references