Behavioral characterization of blocking the ErbB signaling during adolescent and adulthood in reward-liking (preference) and reward-related learning

Abstract

Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting". We demonstrated that chronic administration of the pan-ErbB kinase inhibitor JNJ28871063 (JNJ) to adolescent mice, but not to adult mice, reduced alcohol preference compared with the saline-injected group, without affecting avoidance learning as measured by increasing concentrations of quinine in the bitter avoidance test. Adolescent JNJ-treated mice continue to demonstrate less alcohol preference in adulthood compared with their saline-injected controls. In addition, adolescent JNJ-treated mice and their saline-injected controls did not differ in the time they spent in the food-condition chamber, and in their preference for social odor. In contrast to adolescent JNJ- treated mice, blocking the pathway during adulthood alter the preference to natural reward. These data support our initial findings that interruption of the ErbB pathway during adolescence emerges in a reduced hedonic capacity that persists into adulthood, without disturbing avoidance and reward learning. In addition, this paper provides a further behavioral role of the ErbB signaling pathway in the reward system, and suggests a different time period for the involvement of the pathway in the "liking" and the "wanting" components of the system.

Keywords: Adolescence; Anhedonia-like behavior; Animal models; Conditioned place preference; ErbB signaling; Reward system; pan-ErbB kinase inhibitor.