Differences in response initiation and behavioral flexibility between adolescent and adult rats

Abstract

Adolescence is a period of increased vulnerability to psychiatric illnesses such as addiction, mood disorders, and schizophrenia. Rats provide a useful animal model for investigating the differences in behavior and biology between adults and adolescents that stem from ongoing brain development. We developed the Cued Response Inhibition Task, or CRIT, to assess response inhibition and initiation processes by measuring the ability of rodents to withhold a response during an inhibitory cue and then to respond promptly after cue termination. We found no difference between adult and adolescent rats in the ability to appropriately inhibit a response during cue presentation. Adolescents, however, were unable to initiate a response as quickly as adults after cue termination. Further, we observed that this difference in responding was abolished after adolescent rats aged to adulthood with no additional training. In a separate experiment, adult and adolescent rats were trained in CRIT and then trained in another protocol in which the response inhibitory cue from CRIT was used as a Pavlovian cue predictive of reward. Adolescents demonstrated more reward-seeking behavior during the previously inhibitory Pavlovian cue than adults, indicative of greater behavioral flexibility. Taken together, these data suggest that, compared with adults, adolescent rats (a) are less able to initiate a response after response inhibition, (b) equally inhibit behavioral responses, and (c) are more adept at flexibly switching behavioral patterns. Furthermore, this study characterizes a task that is well suited for future pharmacological and electrophysiological investigations for assessing neuronal processing differences between adolescents and adults.

Figure 1

Schematic detailing the Cued Response Inhibition Task (CRIT). Each trial begins with simultaneous presentation of the nose-poke light and an inhibitory cue (tone), which varies in duration from 5 to 30 s. During this response inhibitory period, a nose-poke response results in termination of all cues and immediate progression to the intertribal interval (ITI). After the response inhibitory cue, rats have a 5-s response period during which responses are reinforced with a pellet. The ITI begins after the rat enters the food trough to collect the pellet. There are three possible trial outcomes: correct responses, premature responses, and omissions. Both premature responses and omissions send the trial directly to the ITI.

Figure 2

During initial acquisition of the Cued Response Inhibition Task (CRIT) (using a 10-s response window), there was no difference between adult and adolescent rats in acquisition of either (A) response inhibition, as assessed by response inhibition ratio (correct/incorrect trials), or (B) omission trials.

Figure 3

(A) Following the shift to the more challenging, 5-s response period version of the Cued Response Inhibition Task (CRIT), there were still no age-related differences in response inhibition. (B) Adolescent rats were less able to respond quickly for reward following inhibitory cue termination, as evidenced by the increased number of omitted responses. Results are displayed from the final 3 days of CRIT training. Displayed: Means and ± SEM.

Figure 4

(A) There were no age-related differences in total nose pokes into the port, trials completed, or trough entries. (B) There was no difference in reaction time to food delivery.

Figure 5

(A) There was no difference between age groups in response inhibition. However, after a 21-day training-free period, allowing the adolescents to age to adulthood, the group that began training as adolescents showed a nonsignificant trend toward improved performance compared with the group that began in adulthood. (B) There were more omission trials during adolescence than during adulthood. After 21 days without training, this group difference was abolished. Data displayed are from the final three sessions of training (left), then the first three sessions after the break (right). Displayed: Means and ± SEM.

Figure 6

(A) Following Cued Response Inhibition Task (CRIT) training, rats performed right sessions of discriminative Pavlovian conditioning using the previously response inhibitory cue as a CS+. Adolescents demonstrated more reward-seeking behavior during the cue than adults. (B) A separate group of rats were trained in discriminative Pavlovian conditioning with no previous cue exposure. There was no difference in reward seeking between groups and no difference in reward seeking following stimulus reversal. The y-axis indicates discriminative responding, which was calculated as time in food trough during the conditional stimulus (CS+) divided by both time in food trough during the CS+ and CS− (CS+/[CS+ + CS−). Displayed: Means and ± SEM.