Decreased dopamine signaling with excessive cocaine use

Excessive cocaine use in rats is associated with decreased signaling of the neurotransmitter dopamine, according to a study published online in Nature Neuroscience. The study resolves an ongoing controversy in the field and suggests a potential therapeutic avenue for treating addiction in people.

Dopamine is involved in the response to rewarding stimuli, including drugs of abuse, such as cocaine.

Ingo Willuhn and colleagues measured the rapid increases in dopamine release in the ventral striatum (a part of the brain’s reward pathway) of rats in response to infusions of cocaine. Rats were allowed to self-administer intravenous cocaine diluted in water for several hours each day. Under these conditions, most, but not all, rats will increase their cocaine intake over time. The authors found that rats that increased their drug intake over time released less dopamine after each hit of the drug; rats with more stable drug intake did not show such a decrease. When drug-induced dopamine release was restored with L-DOPA, a drug used in Parkinson’s disease treatment, rats significantly decreased their cocaine intake.

These findings support the theory that excessive drug use in addicts could be compensating for decreased drug-induced dopamine release as addiction progresses. Further studies are needed to examine whether restoring normal dopamine release with drugs like L-DOPA may prove effective in reducing drug use in human addicts.