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 50kHz 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-responder (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 50kHZ USVs emitted by this phenotype. bHRs emitted increases in 50kHZ 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.

Compromised NMDA/Glutamate Receptor Expression in Dopaminergic Neurons Impairs Instrumental Learning, But Not Pavlovian Goal Tracking or Sign Tracking

“…Supporting this link, we observed that elimination of NMDA receptors on dopamine neurons did not affect pavlovian sign tracking, and previous studies using similar models have also found locomotor sensitization is not dependent upon NMDARs in dopamine neurons ( Engblom et al, 2008 ; Zweifel et al, 2008 ; Luo et al, 2010 ; Beutler et al, 2011 ). Thus, while a host of neural mechanisms likely influence the development of a sign-tracking conditional response ( Flagel et al, 2007, 2010 ; Lomanowska et al, 2011 ; Fitzpatrick et al, 2013 ; Perez-Sepulveda et al, 2013 ; Haight and Flagel, 2014 ), our data indicate that NMDAR activity in dopamine neurons—along with its contribution to phasic dopamine release—is not among these factors.…”

Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system

“…Male (right) and female (left) (A) glutamate levels expressed as ng/mg, and (B) densitometric data for NR2B/actin ratios are displayed. Data expressed as mean ± SEM; ⁄⁄ p < .01 between ACC and EE animals; Male: ACC-Saline, n = 7; ACC-LPS, n = 5; EE-Saline, n = 6; EE-LPS, n = 7; Female: ACC-Saline, n = 7; ACC-LPS, n = 5; EE-Saline, n = 7; EE-LPS, n = 6. lower levels of 'positive' 50-kHz vocalizations which recovered following chronic exposure to EE (Perez-Sepulveda et al, 2013). Notably, animals maintained in EE have been reported as less anxious, compared to standard housing conditions (Baldini et al, 2013;Ravenelle et al, 2013), which may explain the maintained social competency of these animals following MIA.…”

Positive Emotional Learning Induces Resilience to Depression: A Role for NMDA Receptor-mediated Synaptic Plasticity

“…Environmental enrichment has been used to induce resilience to depression in these stress models. Environmental enrichment has been shown to robustly increase positive affect as measured by Hedonic 50-kHz USVs as well as saccharin preference [ 55 , 56 ]. In a similar manner as humans, environmental enrichment induced positive affect leads to resilience to depression in rat exposed to chronic stress [ 55 , 57 ].…”