Faulty Biological Clocks May Influence Addiction

A gene that regulates the body’s circadian rhythms, including sleep and wakefulness, body temperature, hormone levels, blood pressure and heart activity, may also play a central role in drug addiction, according to a study published online by the Proceedings of the National Academy of Sciences (PNAS).

Although expressed primarily in the brain’s circadian command center, biological clock genes have also been found in areas of the brain involved in reward and addiction.

A team led by researchers from the University of Texas Southwestern Medical Center at Dallas and including Northwestern University’s Joseph S. Takahashi, Walter and Mary Elizabeth Glass Professor in the Life Sciences and a Howard Hughes Medical Institute investigator, used mice lacking the Clock gene to examine the possible involvement of the biological clock system in the rewarding properties of cocaine. (In 1997, Takahashi led the team that cloned Clock, the first mammalian circadian gene to be cloned.)

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. (Dopamine is a neurotransmitter associated with the “pleasure system” of the brain, providing feelings of enjoyment from certain activities.)

In addition to Takahashi, other authors on the PNAS paper are lead author Colleen A. McClung, M.D., senior author Eric J. Nestler, M.D., and Donald Cooper, M.D., of UT Southwestern; Martha Vitaterna of Northwestern University; Kyriaki Sidiropoulou of the University of Crete in Heraklion; and Francis J. White of the Rosalind Franklin University of Medicine and Science.

The study was supported by grants from the National Institute on Drug Abuse, the National Institute of Mental Health and the Onassis Public Benefit Foundation.

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