New research clarifies the role of drugs of abuse on sleep, why cocaine is so powerful, and the brain changes that occur due to abuse that make addiction so difficult to treat. The new findings show that:
Sleep, sleep disturbances, and circadian rhythms of our biological clock interact with such neurological diseases as drug addiction.
As a result of cocaine addiction, changes occur within the nucleus accumbens, a brain area involved in reward- and pleasure-motivated behaviors, narrowing the behavioral repertoire to drug-seeking.
Compulsive cocaine-seeking can develop in rats after extended cocaine use, and an alternative reinforcer enhances the animals' tendency to abstain from drug-seeking when punished by a mild electrical foot shock.
Intense sweetness can be more addictive than cocaine.
The changes in neural processing that are induced by cocaine can increase the influence of motor habits and decrease the influence of motivation.
Studies have found that addictive drugs such as cocaine affect many circadian, or biological clock, genes including CLOCK and NPAS2, which have been shown to regulate dopamine, a brain chemical that underlies the rewarding effects of cocaine.
By administering such addictive drugs as alcohol, the narcotic painkiller fentanyl, and nicotine to animals, scientists have been able to entrain laboratory rats to perform behaviors controlled by a circadian timer, such as running on an exercise wheel. Research with human patients has also underscored the connection between sleep disturbances and addiction.
Scientists also have determined that cognitive deficits characteristic of people who regularly use the street drug ecstasy may be based on drug-induced changes in sleep neurobiology. Their altered sleep patterns, cognitive deficits, and impulsivity may be exacerbated by high levels of catecholamines, brain chemicals that the body produces in response to stress.
Studies of former cocaine users demonstrated that they experienced a combination of deficits: They were less vigilant and less able to learn. They also produced deficient sleep EEG recordings. However, these same patients reported that their sleep had improved. Gordon says this disconnect between physiological measures and cognitive self-awareness involved different areas of the brain, including reward and arousal circuits.
Researchers also are trying to identify the neurobiological factors that help explain a recovering addict's vulnerability to relapse.
"Drug addiction is characterized by compulsive drug taking, which occurs even though addicts understand that the behavior is harmful to them. It is also a chronic disorder. Addicts find it extremely difficult to suppress drug taking and often relapse, even after years of abstinence," says Laura Peoples, PhD, of the University of Pennsylvania Medical School.
"The compulsive nature of the behavior and the enduring vulnerability to relapse suggests that drug addiction is accompanied by long-lasting changes in those parts of the brain that underlie motivation and behavioral choice," says Peoples, who will chair a symposium titled "Reconciling Molecular and Electrophysiological Evidence of Cocaine-Induced Neural Plasticity."
In other studies, scientists have developed a model system that provides both positive and negative incentives capable of turning animals away from the pursuit of drugs, says Yann Pelloux, PhD, of the University of Cambridge.
To develop new therapeutic strategies for drug addiction, scientists must study animal models that are not based on simple drug self-administration, Pelloux says. Although data from studies with humans are limited, he says they suggest that the negative consequences of drug abuse persuade individuals to abstain from cocaine. Thus, a wide spectrum of social and nonsocial rewards might help people to shift their focus from illicit drugs, he says. . . .