Impulsivity characterization in the Roman high- and low-avoidance rat strains: behavioral and neurochemical differences

Abstract

The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for rapid vs extremely poor acquisition of active avoidance behavior in a shuttle-box has generated two phenotypes with different emotional and motivational profiles. The phenotypic traits of the Roman rat lines/strains (outbred or inbred, respectively) include differences in sensation/novelty seeking, anxiety/fearfulness, stress responsivity, and susceptibility to addictive substances. We designed this study to characterize differences between the inbred RHA-I and RLA-I strains in the impulsivity trait by evaluating different aspects of the multifaceted nature of impulsive behaviors using two different models of impulsivity, the delay-discounting task and five-choice serial reaction time (5-CSRT) task. Previously, rats were evaluated on a schedule-induced polydipsia (SIP) task that has been suggested as a model of obsessive-compulsive disorder. RHA-I rats showed an increased acquisition of the SIP task, higher choice impulsivity in the delay-discounting task, and poor inhibitory control as shown by increased premature responses in the 5-CSRT task. Therefore, RHA-I rats manifested an increased impulsivity phenotype compared with RLA-I rats. Moreover, these differences in impulsivity were associated with basal neurochemical differences in striatum and nucleus accumbens monoamines found between the two strains. These findings characterize the Roman rat strains as a valid model for studying the different aspects of impulsive behavior and for analyzing the mechanisms involved in individual predisposition to impulsivity and its related psychopathologies.

Figure 1

The mean (±SEM) water intake (panel a) and total licks (panel b) in FT 60 s across 20 sessions of SIP. (^*) Statistical analyses indicate significant differences between RHA-I and RLA-I from that session onward. (#) Significant differences from session 1.

Figure 2

The mean (±SEM) number of choices of the large reward on the delay-discounting task between strains. (^*) Statistical analyses indicate significant differences in delay between RHA-I and RLA-I.

Figure 3

5-CSRT task acquisition of RHA-I and RLA-I rats. The data are the cumulative number of sessions ±SEM required to reach each training stage (see Materials and methods section for details on the training procedure).

Figure 4

Performance of RHA-I and RLA-I on the 5-CSRT task (SD=1): percentage of accuracy (a), percentage of omissions (b), number of premature responses (c), and number of perseverative responses (d). RHA-I rats made more premature responses, while low-avoidance rats made a significant percentage of omissions. Data are means±SEM; (^*) statistical analyses indicate significant differences between RHA-I and RLA-I.

Figure 5

Latency to correct response, incorrect response, and reward RHA-I and RLA-I on 5-CSRT task (SD=1). Data are means±SEM; (^*) statistical analyses indicate significant differences between RHA-I and RLA-I.

Figure 6

DOPAC+HVA/DA and 5-HIAA/5-HT turnover ratios (pmol/mg tissue) in striatum and nucleus accumbens (NAc) in RHA-I and RLA-I rats. Data are means±SEM; (^*) statistical analyses indicate significant differences between RHA-I and RLA-I.

Figure 7

Correlations for RHA-I rats between neurochemical measures and impulsivity assessment. Premature responses on the 5-CSRT task and levels of 5-HIAA in NAc (a), number of choices of the large reward on the delay-discounting task (delay 40) and 5-HIAA/5-HT levels in striatum (b), number of choices of the large reward on the delay-discounting task, delay 20 (—) and delay 40 (- - -) and levels of DA and DOPAC in striatum (c, d).