Emergence of negative affect as motivation for drug taking in rats chronically self-administering cocaine.

Rationale: The role of negative affect as a motivational factor in animal models of drug addiction has been underexplored in the context of cocaine self-administration.

Objectives: The present investigation studied the relationship between magnitude of affective response and quantity of cocaine consumed in order to clarify the affective components that drive drug use in a preclinical model.

Methods: Rats self-administered (SA) cocaine 6 h/day for 14 consecutive days while their ultrasonic vocalizations (USVs) were recorded.

Results: Animals displayed an increase in 50-kHz call rates (indicating positive affect) when their drug levels were rapidly rising and an increase in 22-kHz call rates (indicating negative affect) when forced to abstain. The rate of 50-kHz calls predicted drug consumption during the 1st week of SA, but not week two. Contrarily, there was a strongly predictive positive association between rate of 22-kHz calls and amount of drug consumed during the 2nd week of SA.

Conclusions: Experimental results indicate that after chronic cocaine self-administration, negative affect emerges when animals are deprived of expected drug during withdrawal. Moreover, the increase in USVs indicating negative affect when deprived of drug was directly related to drug intake, concurrent with a decay in the direct relationship between USVs indicating positive affect and drug intake. The present preclinical support for the widely hypothesized shift from positive to negative affect as a salient motivational factor in human drug abuse adds to growing evidence of the unique value of rat USVs for understanding the role of emotion in drug addiction.