High-novelty-preference rats are predisposed to compulsive cocaine self-administration

Area of Science:

• Neuroscience
• Behavioral Science
• Addiction Research

Background:

• Sensation/novelty-seeking is a key marker for human cocaine addiction.
• The role of this trait in addiction vulnerability, specifically whether it precedes or follows addiction development, remains debated.
• Rat models distinguish novelty-seeking based on locomotor activity (high-responder, HR) or place preference (high-novelty-preference, HNP), with differential psychostimulant sensitivity.

Purpose of the Study:

• To investigate if the high-novelty-preference (HNP) trait, distinct from novelty-induced locomotor activity, predicts vulnerability and severity of cocaine addiction-like behaviors in rats.
• To differentiate the roles of distinct sensation-seeking dimensions in the transition to compulsive drug use.

Main Methods:

• Rats were phenotyped for high-responder/low-responder (HR/LR) and high-novelty-preference/low-novelty-preference (HNP/LNP) traits prior to cocaine exposure.
• Following 60 days of cocaine self-administration (SA), rats received an addiction score based on persistence, motivation (progressive ratio breakpoint), and resistance to punishment.
• These behaviors were selected to mirror clinical features of human drug addiction.

Main Results:

• High-novelty-preference (HNP) rats, unlike HR rats, exhibited a predisposition to compulsive cocaine intake.
• HNP rats displayed significantly higher addiction scores compared to LNP rats after protracted cocaine SA.
• This suggests that novelty preference, not just general novelty response, is linked to compulsive drug use.

Conclusions:

• The high-novelty-preference (HNP) trait in rats is a predictor of vulnerability to compulsive cocaine intake and addiction.
• Addiction may involve two distinct phenotypes: a 'drug use prone' phenotype (e.g., HR) initiating use, and an 'addiction prone' phenotype (e.g., HNP) driving compulsive use.
• Understanding these distinct traits offers new insights into the neurobiological factors underlying cocaine addiction.