![]() ![]() Two of these consist of pairs of receptors of the same type-D 1-D 1 and D 2-D 2. Susan George and her team at the University of Toronto have found three additional dopamine receptor complexes. In addition to the D 1-D 2 dopamine receptors, Dr. George and colleagues are the first to link it to dopamine receptors. Although scientists had already been aware of G q, Dr. The specific transducer, called G q, that ties activation of the D 1-D 2 receptor complex to the calcium cascade effects changes in gene expression, protein production, enzyme levels, the cell's firing rate, and its sensitivity to dopamine. The transducer acts as a molecular switch to initiate further biochemical changes. Simultaneous stimulation of the two receptors in a complex results in the activation of a specialized protein, called a transducer, in the cell. When both parts of a D 1-D 2 receptor complex are stimulated, however-something that is likely when dopamine levels surge as a result of exposure to a drug of abuse-the receptor set initiates a modified cascade that releases calcium within the cell. When a D 1 or D 2 receptor is stimulated singly, it incites a train of intracellular biochemical reactions that scientists have mapped. The researchers had previously identified other dopamine receptor complexes, including D 1-D 1, D 2-D 2, and D 5-D 2. ![]() George's team began studies that eventually led to the discovery of a set of receptors that consist of conjoined D 1 and D 2 receptors (see box). ![]() After searching in vain for a sixth receptor, Dr. George's work that dopamine receptors can initiate calcium signaling within the brain, none of the five known dopamine receptors (D 1 to D 5) had been shown to do so. Receptor Complexes Modify Cellular ResponsesĪlthough scientists had established prior to Dr. Stimulation of the two other complexes influences slower acting biological cascades involving cyclic AMP (cAMP). The consequences could include the persistent symptoms and adverse effects of addiction, such as craving and reduced responsiveness to natural rewards.ĭopamine Receptor Complexes Trigger Different Cellular Cascades: Stimulation of the D1-D2 receptor complex (on right) spurs a burst of calcium within the cell-activating the neuron, making the cell more prone to firing again, and ultimately forging new neural connections. Because the cells use calcium to build and strengthen synaptic connections to other neurons, such bursts, when repeated in the setting of chronic drug abuse, can potentially rewire neural pathways that affect learning, memory, emotions, and other responses. When stimulated by the neurotransmitter, these receptors set in motion a cascade of events leading to a burst of calcium from stores within nerve cells. Susan George and colleagues at the University of Toronto identified a set of previously unrecognized dopamine receptors in a brain area called the striatum. These dopamine surges are transient, but NIDA-funded researchers recently identified a mechanism whereby they may promote long-lasting or permanent changes in behavior and cognition.ĭr. Drugs of abuse trigger abrupt, massive increases in levels of the neurotransmitter dopamine that give rise to intense feelings of reward and reinforcement-the drug high-by temporarily altering the activity levels of dopamine-responsive neurons. ![]()
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