Dopamine

Dopamine has many functions in the brain. Most importantly, dopamine is central to the reward system.

Dopamine neurons are activated when an unexpected reward is presented. In nature, we learn to repeat behaviors that lead to unexpected rewards. Dopamine is therefore believed by many to provide a teaching signal to parts of the brain responsible for acquiring new motor sequences, i.e., behaviors.

Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate proactively perform certain activities. Dopamine is released by naturally rewarding experiences such as food, sex, use of certain drugs and neutral stimuli that become associated with them….

Mesolimbic Dopamine Neurons

Dopamine is one of a number of neurotransmitters found in the central nervous system. Dopamine has received special attention from psychopharmacologists because of its apparent role in the regulation of mood and affect and because of its role in motivation and reward processes. Although there are several dopamine systems in the brain, the mesolimbic dopamine system appears to be the most important for motivational processes. Some addictive drugs produce their potent effects on behavior by enhancing mesolimbic dopamine activity.

Normal Dopamine Activity

Cells in the mesolimbic dopamine system are spontaneously active -- action potentials are constantly generated at a slow rate. This releases small amounts of dopamine into the synaptic cleft. The levels of dopamine produced when the cells are active at this low rate may be responsible for maintaining normal affective tone and mood. Some scientists speculate that some forms of clinical depression may result from unusually low dopamine levels.

Heroin-Enhanced Dopamine Activity

Heroin increases the neuronal firing rate of dopamine cells. The increased number of action potentials produce an increase in dopamine release. The increased dopamine activity increases the effects mediated by postsynaptic dopamine. The heroin user experiences the enhanced dopamine activity as mood elevation and euphoria. When the pharmacological action terminates (i.e., the heroin is eliminated from the brain), the drug user is highly motivated to repeat this experience.

Cocaine-Enhanced Dopamine Activity

Cocaine inhibits the reuptake of dopamine. This increases the availability of dopamine in the synapse and increases dopamine's action on the postsynaptic neurons. The enhanced dopamine activity produces mood elevation and euphoria. Cocaine's effect is usually quite short, prompting the user to repeatedly administer cocaine to re-experience its intense subjective effects.

Combined Heroin- and Cocaine-Enhanced Dopamine Activity

Because heroin and cocaine work on different parts of the mesolimbic dopamine neurons, they can be combined to produce even more intense dopamine activation. (The heroin increases cell firing and dopamine release, while the cocaine keeps the released dopamine in the synaptic cleft longer thereby intensifying and prolonging its effects) .

The combination of heroin and cocaine is known by users as a "speed-ball." This combination of drugs is extremely dangerous, and users show very rapid psychological and physiological deterioration.

Although speed-ball use produces extremely intense activation of brain reward systems, it is often short-lived because this drug combination is associated with a very high fatality rate. The combination of cocaine and heroin is perhaps the most dangerous form of illicit substance use; even cocaine and heroin addicts usually avoid this combination of drugs.

Neuroadpative Effects

In addition to their acute effects described above, repeated use of psychomotor stimulants like cocaine and opiates like heroin produces changes in the mesolimbic dopamine system. Specifically, repeated use of cocaine or heroin can deplete dopamine from this system. These dopamine depletions may cause normal rewards to lose their motivational significance (i.e., produce motivational toxicity). At the same time, the mesolimbic dopamine system becomes even more sensitive to pharmacological activation by psychomotor stimulants and by opiates (i.e., sensitization develops). These neuroadpative changes are probably critical for producing an addiction. Substances that activate the mesolimbic dopamine system without producing these neuroadaptive effects are probably not truly addictive.