Cocaine brain, effects

Amphetamines and cocaine work the same way in the body, but cocaine is much more vigorous at blocking the reuptake of dopamine. How cocaine works is illustrated in Figure 14.26. The great buildup of dopamine in synaptic clefts in the brains reward center is the source of cocaines euphoric effect. As cocaine keeps dopamine from being reabsorbed by the presynaptic neuron, the dopamine remains active in the synaptic cleft, and as a result the reward center stays stimulated. This euphoric state is only temporary, however, because enzymes in the deft metabolize, and hence deactivate, the dopamine. Once the cocaine is metabolized by enzymes, dopamine reuptake is again permitted. By this time, however, there is very little dopamine in the deft to be reabsorbed. Nor is there an adequate supply of dopamine in the presynaptic neuron, which is unable to make sufficient quantities of dopamine without the recycling process. The net result is a depletion of dopamine that causes severe depression. 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

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