Role of individual and developmental differences in voluntary cocaine intake in rats

Abstract

Rationale: Early-onset drug taking is associated with increased likelihood of addiction, but it is unclear whether early onset is causal in development of addiction. Many other factors are associated with increased risk of addiction and also promote early intake. Here, a rodent model is used to explore the causality of early onset in development of self-administration and addiction-like behavior and to examine factors that promote self-administration.

Methods: We used cocaine self-administration to examine drug taking and addiction-like behavior in adolescent and adult rats a priori characterized for their locomotor responses to novelty and cocaine and behavior in the light-dark task.

Results: Adolescent animals initially sought more cocaine than adults. However, as the adolescents matured, their intake fell and they did not differ from adults in terms of unreinforced lever-pressing, extinction or reinstatement behavior. For both age groups, self-administration was positively correlated with the locomotor response to novelty, the locomotor response to cocaine, and with time in light in the light-dark task. The rats that were insensitive to cocaine's locomotor effects and that spent the least time in light in the light-dark task sought the least cocaine, appearing to be "protected" from the reinforcing effects of cocaine. There was no difference between the two age groups in appearance of this "protected" phenotype.

Conclusions: These results suggest that early onset of drug taking may promote increased use, but does not promote progression to addiction-like behavior. Furthermore, protective factors, such as innate anxiety and insensitivity to cocaine's pharmacological effects, function across developmental stages.

Fig. 1

Experimental time line. See Methods section for details

Fig. 2

Time courses of a infusions earned, b active lever presses, and c lever pressing during CNA periods during the 20 sessions of the 40–15 self-administration protocol. Asterisk, significant age effect

Fig. 3

Cocaine concentration in brain homogenate (ng/g) in adolescent and adult rats at 1 and 10-min post-i.v. infusion. Asterisk, significantly different from 1-min group

Fig. 4

Correlations between active lever pressing and a novelty locomotion; b cocaine locomotion; and c time in light in light dark task. Open circles, adolescent animals, closed squares, adult animals

Fig. 5

Interaction between behavior in the light–dark task and locomotor response to cocaine predicts active lever pressing. Asterisks and solid line, low-anxiety animals; triangles and dashed line, high-anxiety animals, based on median split of time in light in light–dark task. (Full model R²=0.37; p=0.0002.)