Dopamine is a neurotransmitter that serves as a chemical messenger in the nervous system and permits individual nerve fibers (neurons) to communicate with each other. The dopamine neurotransmitter belongs to the class of compounds known as monoamines, and more specifically to a subclass of chemicals called catecholamines. Dopamine can act either as an inhibitory mechanism or an excitatory mechanism in the nervous system, depending on the location of dopamine neurons, and the receiving characteristics of the next neuron in the chain.
Dopamine activation has long been associated with increased motor output (i.e., increased physical activity) (Wise 2004). Hence, it is not surprising that dopamine depletion is associated with a variety of movement disorders, such as Parkinson’s disease. Characterized by tremors, muscle rigidity, and lack of fine motor skills, Parkinson’s is caused by a degeneration of dopamine projection fibers originating in a brain region called the sub-stantia nigra. The fact that the administration of a substance (L-DOPA) that increases dopamine synthesis in this brain region is the primary approach to treating Parkinsonism underscores the importance of dopamine in the regulation of motor control and movement.
Changes in dopamine activity also are linked to the expression of certain psychological disorders, such as schizophrenia. Schizophrenia is characterized by shifting, illogical thought patterns, delusional thought processes, and hallucinations. The dopamine hypothesis of schizophrenia suggests that higher than normal levels of dopamine in the midbrain region of patients suffering from schizophrenia produce a biochemical imperative to engage in disordered behavior. Consistent with this position, the most commonly prescribed, and arguably the most effective, drug therapies for schizophrenia are dopamine receptor blockers. A compound labeled chlor-promazine (trade name Thorazine) is especially effective in reducing the symptoms of schizophrenia, and such dopamine antagonists when continued after treatment substantially lessen the chances for relapse compared to cases in which patients stop taking the drug.
There is evidence that blockade of dopamine transmission is associated with the devaluation of incentive systems, perhaps by affecting memory consolidation (Robbins and Everitt 2006). For instance, it is known that stamping-in of stimulus-response associations is blunted under conditions of reduced dopamine activity. Even once a behavior is learned, evidence shows that the ability to retrieve previously acquired information is reduced. Although the precise mechanisms responsible for these challenges to associative processes is not clear, it is clear that reward-seeking is diminished when dopamine systems are compromised.
There is a large literature that shows that a variety of rewarding events elevate the levels of dopamine in pleasure pathways of the brain. There are three major systems that are rich in dopamine fibers: the nigrostriatal system, the mesolimbic system, and the mesocortical system. Of the three, the pathway that has received the most attention from investigators of reward systems is the mesolim-bic pathway. The dopamine projection neurons of the mesolimbic system originate in the ventral tegmental area of the midbrain and terminate in several forebrain regions, most importantly the nucleus accumbens. At one time it was believed that the nucleus accumbens constituted "reward central" and any events or substances that increased dopamine activity in this region served as rewards (Wise and Bozarth 1987). It is now known that other pathways and neurotransmitters are involved in defining reward properties, but the scientific community still maintains that elevated levels of dopamine in the nucleus accumbens contribute prominently to the rewarding effects associated with a variety of motivational processes, including the sex drive and hunger (Berridge and Robinson 1998).
Although dopamine plays a role in mediating a broad array of reinforcing (reward) activities, the topic that has been studied most is the modulatory role played by dopamine in determining the rewarding effects of psy-choactive drugs. While dopamine is important for drugs such as heroin, marijuana, and alcohol, it does not appear to be crucial with respect to determining the reward value of these types of drugs. It is certain, however, that dopamine is the major neurotransmitter involved in defining the potency and addiction potential of psycho-stimulants such as cocaine and amphetamine. With respect to cocaine, the drug blocks the action of the dopamine transporter (DAT) in the nucleus accumbens. DAT is the reuptake chemical in the synaptic cleft (space between neurons where neuro-transmitters are released) that moves dopamine back inside the releasing neuron and restores dopamine levels. When DAT is blocked by cocaine, dopamine remains in the cleft and continues to stimulate the postsynaptic neuron, thus producing euphoria. Amphetamine operates similarly to block dopamine reuptake, but also increases the frequency and amount of dopamine release.
