POSTED 2 JUN 2005
Opium, 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.
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.
Mu receptors, the best-known, occur on both major flavors of neurons (nerve cells): excitatory and inhibitory. The names are descriptive. 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.
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.
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).
Courtesy Dezhi Liao, University of Minnesota
Could there be cannabis receptors in the brain?
Megan Anderson, project assistant; Terry Devitt, editor; S.V. Medaris, designer/illustrator; David Tenenbaum, feature writer; Amy Toburen, content development executive