Decline of prefrontal cortical-mediated executive functions but attenuated delay discounting in aged Fischer 344 × brown Norway hybrid rats.

Despite the fact that prefrontal cortex (PFC) function declines with age, aged individuals generally show an enhanced ability to delay gratification, as evident by less discounting of delayed rewards in intertemporal choice tasks. The present study was designed to evaluate relationships between 2 aspects of PFC-dependent cognition (working memory and cognitive flexibility) and intertemporal choice in young (6 months) and aged (24 months) Fischer 344 × brown Norway F1 hybrid rats. Rats were also evaluated for motivation to earn rewards using a progressive ratio task. As previously reported, aged rats showed attenuated discounting of delayed rewards, impaired working memory, and impaired cognitive flexibility compared with young. Among aged rats, greater choice of delayed reward was associated with preserved working memory, impaired cognitive flexibility, and less motivation to work for food. These relationships suggest that age-related changes in PFC and incentive motivation contribute to variance in intertemporal choice within the aged population. Cognitive impairments mediated by PFC are unlikely, however, to fully account for the enhanced ability to delay gratification that accompanies aging.

Air puff-induced 22-kHz calls in F344 rats.

Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders.

Lewis rats have greater response impulsivity than Fischer rats.

Impulsivity, a tendency toward immediate action without consideration of future consequences, is associated with a wide array of problematic behaviors. Response impulsivity, a type of behaviorally-assessed impulsivity characterized by behavioral disinhibition, is also associated with health risk behaviors. Response impulsivity is distinct from choice impulsivity, which is characterized by intolerance for delay. Lewis rats have higher levels of choice impulsivity than Fischer rats (Anderson & Woolverton, 2005; Madden et al., 2008; Stein et al., 2012). However, no studies have examined whether Lewis and Fischer rats have different levels of response impulsivity. The present research examined response impulsivity in the two rat strains. Subjects were 16 male Lewis and Fischer rats. Rats' response impulsivity was measured using the Five Choice Serial Reaction Time Task (5-CSRTT). In addition, their locomotor activity was measured in locomotor activity chambers. Lewis rats had more premature responses than Fischer rats during the 5-CSRTT assessment [F(1, 14)=5.34, p<0.05], indicating higher levels of response impulsivity. Locomotor activity did not differ between rat strain groups [F(1, 14)=3.05, p=.10], suggesting that overall movement did not account for group differences in response impulsivity on the 5-CSRTT. It can be concluded from this research that Lewis rats have higher levels of response impulsivity than Fischer rats, and therefore provide a valid rat model of individual differences in impulsivity.

Delay discounting in Lewis and Fischer 344 rats: steady-state and rapid-determination adjusting-amount procedures.

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.

Responding in a test of decision-making under risk is under moderate genetic control in the rat.

BACKGROUND: Risk-taking, measured with laboratory tasks such as the Balloon Analog Risk Task (BART), is associated with real-life manifestations of risky behaviors, which may be an important component of inherited liability to alcohol use disorders. To identify genomic factors that influence these traits, the current study (i) characterized performance of a rodent version of the BART in multiple inbred rat strains, (ii) tested the degree to which performance was under genetic control, (iii) explored sex differences in performance, and (iv) evaluated the risk-taking behavior of F1 progeny of high-risk- and low-risk-taking strains to examine modes of inheritance. METHODS: Male and female rats (N = 100) from 5 inbred strains (Wistar-Furth, Fischer-344, Lewis, Spontaneously Hypertensive, Brown Norway) and Wistar-Furth × Fischer-344 hybrids were tested in the rat-BART, as well as in tests of locomotor activity, sucrose preference, and general motivation. RESULTS: About 55% of the variance in risk-taking behavior was attributable to heritable factors. The Fischer-344 strain was the most risk-taking and the most variable in responding. The mating of low-risk-taking Wistar-Furth and Fischer-344 rats produced progeny that behaved most like the Fischer-344 strain. Consistent with prior research in this laboratory (Jentsch et al., 2010), all rats were sensitive to changes in both risk and reinforcement parameters in the rat-BART; rats decreased voluntary risk-taking in the face of increasing risk and increased lever pressing when reinforcement probabilities were reduced. CONCLUSIONS: Our results endorse a moderately heritable pattern of risk-taking behavior in rats. The behavior of the hybrid progeny suggests a polygenic model with most gene effects transmitted by mode of dominant inheritance. The identification of high-risk and low-risk strains allows for isolation of quantitative trait loci associated with task performance and for probing the relationships between risk-taking and dimensions of alcohol use disorders.

Dose preference and dose escalation in extended-access cocaine self-administration in Fischer and Lewis rats.

RATIONALE: Drug addiction is a disease with a genetic component that may be involved in different stages of its progression. Cocaine users escalate unit doses and frequency of self-administration events in naturalistic settings. Rats that self-administer drugs of abuse over extended sessions increase the number of infusions over days. OBJECTIVES: Comparison of two genetically different inbred rat strains, Fischer and Lewis, in a new self-administration paradigm whereby rats select between different unit doses of cocaine, thus potentially escalating the unit dose and the number of infusions. METHODS: Extended (18 h/day) self-administration sessions lasted for 14 days. Rats had access to two active levers associated with two different unit doses of cocaine. If a rat showed preference for the higher unit dose, then the available doses were escalated in the following session. Four cocaine unit doses were available (0.2, 0.5, 1.25, and 2.5 mg/kg/infusion). RESULTS: Lewis rats showed a clear preference for the two higher doses of cocaine (70% of rats), with a high percentage (35%) of the individuals escalating to the highest unit dose, and escalated the total amount of cocaine taken over days. Fischer rats, however, preferred the two lower doses (63%) and did not escalate the amount of cocaine taken over days. Fischer, but not Lewis, rats showed an activated hypothalamic-pituitary-adrenal axis in acute withdrawal (24 h). CONCLUSION: This work shows the power of a model of extended-access self-administration that allows for the subject-controlled dose-escalation of the unit dose of cocaine, and underlines the genetic differences that modulate cocaine intake.

Maternal environment alters social interactive traits but not open-field behavior in Fischer 344 rats.

Although it is recognized that the genetic background governs behavioral phenotypes, environmental factors also play a critical role in the development of various behavioral processes. The maternal environment has a major impact on pups, and the cross-fostering procedure is used to determine the influence of early life experiences. The present study examined the influence of maternal environment on behavioral traits in inbred Fischer 344 (F344) rats. F344/DuCrlCrlj and Wistar (Crlj:WI) pups were fostered from postnatal day 1 as follows: Wistar pups raised by Wistar dams, F344 raised by Wistar, Wistar raised by F344, and F344 raised by F344. At 10 weeks of age, rats were randomly assigned to an open-field test and social interaction test. In the open-field test, irrespective of the rearing conditions, the activity during the first 1 min was significantly lower in F344 rats than in Wistar rats. Latency to the onset of movement showed no difference between groups. In the social interaction test, the recognition performance during the first 1 min in F344 raised by F344 was significantly shorter than that in the other groups. The onset of recognition to a novel social partner in F344 raised by F344 was significantly delayed, and the delay disappeared upon cross-fostering by Wistar dams. These results raise the possibility that the behavioral phenotype of F344 rats results from the interplay of genetic factors and maternal environment during early life, and that F344 rats are a strain with high susceptibility to rearing conditions for the formation of their emotionality.

Strain difference in behavioral response to a new environment in rats.

Locomotor activity in rats throughout a 24-hour period in a new environment was examined for strain differences and for the capacity for adaptation to that environment. Fischer 344 rats (F344), spontaneously hypertensive rats (SHR) and Wistar normotensive Kyoto rats (WKY) were used. The horizontal locomotor activity of individual rats was measured by photocell-utilizing activity-recording devices. The locomotor activity counts on the second day, after 1 day of adaptation, were compared with those after 5 days of adaptation (on the sixth day). In WKY, there was no difference in activity at any period of the day between the second and sixth days. In SHR, the locomotor activity on the second day between 6:00 h and 9:00 h (in the light phase) and between 24:00 h and 3:00 h (in the dark phase) was higher than on the sixth day. In F344, the locomotor activity on the second day between 18:00 h and 2:00 h was higher than on the sixth day. The capacity for adaptation in SHR and F344 was thus poorer than in WKY. The poor adaptation in SHR and F344 was similar to that in depressive patients induced by moving house. These findings suggested that SHR or F344 were suitable for depression research.