Differential impact of a complex environment on positive affect in an animal model of individual differences in emotionality

Abstract

Anhedonia, or the inability to experience positive feelings is a hallmark of depression. However, few animal models have relied on decreased positive affect as an index of susceptibility to depression. Rats emit frequency-modulated ultrasonic vocalizations (USVs), designated as "positive" calls in the 50-kHz range. USVs have been associated with pharmacological activation of motivational reward circuits. Here we utilized selectively-bred rats differing in "emotionality" to ask whether there are associated differences in USVs. Rats bred based on locomotor response to novelty and classified as bred High Responders (bHRs) or bred Low Responders (bLRs) exhibit inborn differences in response to environmental cues, stress responsiveness, and depression-like behavior. These animals also exhibit differences in anxiety-like behavior, which are reversed by exposure to environmental complexity (EC). Finally, these animals exhibit unique profiles of responsiveness to rewarding stimuli accompanied with distinct patterns of dopamine regulation. We investigated whether acute and chronic environmental manipulations impacted USVs in bHRs and bLRs. We found that, relative to bLRs, bHRs emitted significantly more 50-kHz USVs. However, if a bLR is accompanied by another bLR, there is a significant increase in 50-kHZ USVs emitted by this phenotype. bHRs emitted increases in 50-kHZ UVSs upon first exposure to EC, whereas bLRs showed a similar increase only after repeated exposure. bLRs' increase in positive affect after chronic EC was coupled with significant positive correlations between corticosterone levels and c-fos mRNA in the accumbens. Conversely, a decline in the rate of positive calls in bHRs after chronic EC was associated with a negative correlation between corticosterone and accumbens c-fos mRNA. These studies demonstrate that inborn differences in emotionality interact with the environment to influence positive affect and underscore the potential interaction between glucocorticoids and the mesolimbic reward circuitry in modulating 50-kHz calls.

Keywords: affect; emotionality; individual differences; ultrasonic vocalization.

Figure 1

A) Chronic exposures where 30-minutes long every other day (labeled by each individual stand-up line in the diagram) throughout a three-week period. Acute exposures were performed on the last day of chronically exposed animals. On the last day blood was drawn for CORT analysis 20 minutes after exposure and brains were collected for in situ hybridizations studies (upside down arrow). (n=6 animals per group). B) Representative sonogram depicting frequency modulated 50-kHz USV calls.

Figure 2

A) Individual bHR animals elicit a higher number of calls relative to single bLRs in the control cage. (n= 6 per group; *p<0.05) *** t-test pair-wise comparison from animals. B) bHRs show a significant increase in 50 kHz USVs when exposed to a complex environment. Presence of a cage mate also increased USVs in bHR. C) bLR animals show a significant increase in the number of 50 kHz USVs when accompanied by another bLR when acutely exposed to a control environment or EC. (*p<0.05) (**p<0.01) bonferroni post-hoc pair-wise comparisons.

Figure 3

Chronic EC increases 50 kHZ USVs in bLRs and not bHRs. A) bHRs show no significant differences in 50 kHz USVs when exposed to EC under chronic conditions relative to controls. B) Conversely, bLR animals chronically exposed to EC showed a significant increase in the number of 50 kHz USVs. C) USVs responses to EC are weakened by repeated exposures in bHRs were an initial increase is lost upon repeated exposure. D) bLR showed an opposite trajectory in their USV response to chronic EC, where an increase emerged towards the end after repeated exposures (*p<0.05) (**p<0.01) bonferroni post-hoc pair-wise comparisons.

Figure 4

Exposure to a complex environment reverses bHR and bLR differences in locomotion, social interaction, and aggression. A) bHRs exposed to chronic EC showed significantly lower locomotion relative to chronic bHR controls. Thus, chronic EC reverses innate differences between the phenotypic groups where bHRs displayed the same levels of locomotion relative to bLRs. B) Exposure to EC decreases social behavior in bHRs, which reverses phenotype differences in acute and chronic EC exposed animals (n= 6 animals per group; *p<0.01). C) Exposure to EC reduces the significantly high levels of aggression seen in bHR under chronic exposure to a control cage. Such reversal disrupts phenotype differences between bHR and bLR under chronic EC conditions (*p<0.05; **p<0.01) bonferroni post-hoc pair-wise comparisons.

Figure 5

bHR animals exhibited a differential significant increase in CORT upon chronic exposure to EC relative to all groups. An interaction effect showed that chronic EC differentially increased CORT in bHRs relative to bLRs, thus after chronic EC bHRs showed significantly higher levels of CORT relative to chronic EC bLRs (*p=0.001).

Figure 6

Bivariate correlations of CORT and accumbens c-fos expression for bHR and bLR animals exposed to chronic EC. bLRs displayed a distinct pattern of correlation of CORT with c-fos in the accumbens (Core: r=0.89 and Shell: r=0.73; p=0.009 and p=0.05 respectively), whereas bHR exposed to chronic EC displayed an opposing pattern were CORT correlates negatively with the accumbens c-fos expression (Core: r=−0.79 and Shell: r=−0.83; p=0.03 and p=0.02 respectively).

Figure 7

Representative images of c-fos expression for quantified regions; (Sh; Shell, NAcC; Core, IL; Infralimbic, PL; Prelimbic, dPAG; dorsal Periacueductal Gray.