Neurobiological Changes Related to Cocaine Use

Neurobiological Changes Related to Cocaine Use

Cocaine has effects on multiple neurotransmitters, including re-lease and reuptake blockade of dopamine, serotonin (5-hydrox-ytryptamine [5-HT]) and norepinephrine. The most widely ac-cepted explanation of cocaine-induced euphoria is that dopamine reuptake inhibition results in increased extracellular dopamine concentration in the mesolimbic and mesocortical reward pathways in the brain. Another important phenomenon related to acute cocaine administration is that of “acute tolerance”. A single dose of cocaine has been shown experimentally to reduce the response to a second identical dose given 100 minutes later as measured by extracellular dopamine levels and motor activity (Bradberry, 2000). The finding of “acute tolerance” is consistent with the binge pattern of cocaine use in which abusers consume escalating doses of cocaine in an attempt to recapture the intense euphoria of the initial cocaine dose (Bradberry, 2000). A growing body of evidence indicates that chronic cocaine administration can result in sustained neurophysiological changes in brain sys-tems that regulate psychological processes, specifically pleasure and hedonic responsivity. This has been postulated to underlie a physiological addiction to cocaine with associated withdrawal phenomena that are manifested clinically as a psychological syn-drome (Koob and Nestler, 1997).