Neuroscience

Punishment (psychology)

Prefrontal cortex

Central nervous system

Developmental psychology

Cognition

Psychology

Nucleus accumbens

Orbitofrontal cortex

Self-administration

Brain stimulation reward

Anesthesia

Addiction

Medicine

Proceedings of the National Academy of Sciences

Significance Addiction is characterized by compulsive drug use despite negative consequences. In a rat model of methamphetamine self-administration, we found that compulsive-like drug taking was correlated with alterations in the balance between an increased orbitofrontal cortex-dorsomedial striatal “go” circuit and a decreased prelimbic cortex-ventrolateral striatal “stop” circuit only in an addictive-like subgroup resistant to foot shock punishment paired with drug taking. In nonaddictive-like rats, the go-stop balance, which was similarly changed after repeated self-administration without punishment, normalized toward baseline levels after punishment. These results indicate that restoring the go-stop physiological balance, perhaps with noninvasive brain stimulation, may provide a promising avenue for addiction treatment when coupled with neuroimaging to assess clinical responses to determine the adequacy of a course of treatment.

Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals