Biological Clock and Drug Addiction

Problems with a sense of time -
problems with cocaine. In mice.

The Clock gene not only controls the body's circadian rhythms, including sleep and wakefulness, body temperature, hormone levels, blood pressure and heart activity, it may also be a key regulator of the brain's reward system.

UT Southwestern researchers showed that, in mice, the Clock gene regulates the reward response to cocaine, suggesting that similar actions take place in humans. "We found that the Clock gene is not only involved in regulating sleep/wake cycles, but is also very involved in regulating the rewarding responses to drugs of abuse," said Dr. Colleen A. McClung, assistant instructor of psychiatry at UT Southwestern and the study's lead author. "It does so through its actions on dopamine pathways."

In the study, mice that lacked the Clock gene were injected with cocaine. Not only did the mice experience problems with their circadian cycles - not sleeping as much and becoming more hyperactive - they also found cocaine more rewarding than control mice, demonstrated by their strong preference for the location where the drug was administered.

In addition, Clock-deficient mice produced more dopamine than control mice did, suggesting that the gene controlling circadian rhythms is a key regulator of the brain's reward system and may influence the addictive properties of drugs such as cocaine.

"We tracked dopamine cells in the mice brains and found that these cells fired more rapidly and showed a pattern called bursting, which leads to a usually large dopamine release," Dr. McClung said. "We also found that more dopamine is produced and released in these mice under normal conditions and particularly after exposure to cocaine."; Source: UT Southwestern Medical Center