The Why Files The Why Files --

Brain on drugs... The science of drug receptors

Feeling inhibited?
Small dish filled with black raw opium gumOpium, a gum exuded by the poppy flower, was one of the first plants known to affect the brain; the ancient Greeks called it "happiness plant." When opium locks to opiate receptors, it dampens pain, causes euphoria and triggers some of the brain's strongest reward systems. That makes opiates (including opium and the more powerful morphine and heroin) the drug of choice for millions of addicts.

Newly harvested raw opium gum. Photo: CIA

The puzzle of how opiates affect the brain started unraveling when Solomon Snyder and Candace Pert of Johns Hopkins University discovered the first opiate receptor in 1973. Now, three related forms of the receptor -- mu, delta and kappa -- are found in different body locations.

Graphic of how opiates stimulate positive emotional feelings.
Three neurons engage in opiate action. When opiates bind to opiate receptors, a signal goes to the dopamine terminal (shown here as part of another neuron) to release dopamine. Dopamine binds to dopamine receptors, stimulating the post-synaptic cell and a positive emotional feeling. Graphic: NIDA

Mu receptors, the best-known, occur on both major flavors of neurons (nerve cells): excitatory and inhibitory. The names are descriptive.  Image of brain with three areas highlighted.Excitatory neurons, "Make the other neurons more active, while inhibitory neurons make the whole circuit go down," observes Dezhi Liao, an assistant professor of neuroscience at the University of Minnesota. Researchers have found that endogenous opioids reduce inhibition of inhibitory neurons. Like "I don't have no money," two negatives sum to a positive, and the neural network becomes more active.

A.) Opiates affect the limbic system, which controls emotions, increasing pleasure, relaxation and contentment. B.) The brainstem controls automatic activity, like breathing or coughing. Opiates can act on the brainstem to stop coughing or slow breathing. C.) The spinal cord transmits pain signals from the body. Opiates act here to block pain messages. Diagram: NIH

But Liao observes that "The mu opiate receptor is almost everywhere, especially on excitatory neurons." How might opiates affect excitatory neurons? In lab dishes, Liao with Horace Loh, of the University of Minnesota's Basic Research Center on the Molecular and Cell Biology of Drug Addiction, showed that opiates also inhibit the excitatory neurons, which reduces activity in the circuit. "If you constantly put morphine on excitatory neurons, it will suppress the function, and make fewer excitatory synapses [connections]," he says.

Map of world with opium producing areas highlighted
Countries where opium poppy is grown. Map: CIA

The morphine bath reduced the number of dendritic spines, tiny protrusions that connect nerve cells. The receptor seems to cause the decline, Liao says, because the spines did not change in mice lacking a gene for the mu opiate receptor, and they grew in normal mice given a chemical blocker for opiate receptors.

Liao concluded that while some level of endogenous opioid is needed to keep excitatory neurons healthy, the drug morphine "changes the structure of excitatory synapses. If someone constantly takes morphine, eventually it will damage the brain, change its structure and function," Liao says (see "Mu-opiate Receptors..." in the bibliography).

Black and white image of nerves snaking like rivers.
Dendritic spines connect neurons. In time-lapse images, treatment with morphine decreased the number of spines (arrows). Courtesy Dezhi Liao, University of Minnesota

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Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive

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