For millions of drug addicts, life is a vicious cycle of recovery and relapse. Drugs such as cocaine trigger the brain to churn out dopamine, a chemical that gives the "high." Now research with mice shows that dopamine production can also be stimulated by extreme stress, and that may be what leads recovering addicts to take more drugs.
In the last decade, researchers studying a range of addictive drugs have come to the same conclusion: Addiction and relapse are somehow linked to dopamine production. In previous work, neuroscientist Robert Malenka of Stanford University in Palo Alto, California, discovered that cocaine amplifies the neural signal that leads to dopamine production.
Curious to see if other kinds of drugs have the same effect, Malenka and researchers from the University of California, San Francisco, dosed mice with uppers (cocaine, amphetamines, and nicotine) and downers (morphine and ethanol). After 24 hours, the team collected thin slices of the midbrain, where dopamine is produced, applied an electrical current to simulate the passage of a brain message, and measured the strength of resulting synaptic signals. All five drugs, they found, had temporarily boosted the signal that triggers dopamine production by almost twofold.
The team then evaluated the effects of another known trigger for drug abuse and relapse--extreme stress. They had normal mice swim in frigid water; brain samples collected 24 hours later showed amplified synaptic signals for dopamine, as if the mice had taken a dose of cocaine. Then the team used a chemical to block the body's response to stress, and the mice endured the swim without a surge of dopamine, as the authors describe in 20 February issue of Neuron. Repeated exposure to stress and drugs makes the brain churn out dopamine too easily, Malenka says, and that may explain why stress often leads to relapse among drug abusers.
The fact that stress and five very different drugs caused the same effects means we're "on to something fundamental about the biology of addiction," said neuroscientist Julie Kauer of Brown University in Providence, Rhode Island. The research backs up her belief that addictive drugs alter brain chemistry, perhaps permanently.