The role of the anterior insula during targeted helping behavior in male rats

Cox, Stewart S.; Kearns, Angela; Woods, Samuel K; Brown, Brogan J.; Brown, Samantha J.; Reichel, Carmela M.

doi:10.1038/s41598-022-07365-3

Cited by 16 publications

(19 citation statements)

References 57 publications

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“…The present study also lacks an “empty” virus control group to test for CNO effects alone (Experiment 2). In a previous study, we demonstrated that the same CNO dose did not have an impact on social behavior (identical task) or impact cued meth seeking [45, 46]; and CNO injections did not alter oxytocin secretion or social behavior [41]. Finally, Experiment 1 included male subjects only and Experiment 2 was not powered to detect sex differences, but our results from Experiment 2, while preliminary, do not indicate a sex effect of PVN oxytocinergic neuron activation or inhibition on cued heroin seeking.…”

Section: Discussionmentioning

confidence: 99%

“…In Experiment 2, rats participated in a social interaction task to assess the impact of DREADD-induced excitation and inhibition of PVN oxytocinergic neurons on social interaction (similar to our previously published studies [44, 45]). The social interaction task began 1 week into the abstinence period.…”

Section: Methodsmentioning

confidence: 99%

“…Free-floating sections were immunohistochemically labeled for c-fos (fos), an immediate early gene used as a marker of neuronal activity, as in our previous publications [45, 46]. In Experiment 1, we used a DAB stain approach to label fos in various PVN projection areas.…”

Section: Methodsmentioning

confidence: 99%

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Paraventricular Nucleus of the Hypothalamus Oxytocin and Incubation of Heroin Seeking

et al. 2023

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Introduction: There are numerous pharmacologic treatments for opioid use disorder (OUD), but none that directly target the underlying addictive effects of opioids. Oxytocin, a peptide hormone produced in the paraventricular nucleus of the hypothalamus (PVN), has been investigated as a potential therapeutic for OUD. Promising preclinical and clinical results have been reported, but the brain region(s) and mechanism(s) by which oxytocin impacts reward processes remain undetermined. Methods: Here, we assess peripherally administered oxytocin’s impacts on cued reinstatement of heroin seeking following forced abstinence and its effects on neuronal activation in the PVN and key projection regions. We also examine how DREADD-mediated activation or inhibition of oxytocinergic PVN neurons alters cued heroin seeking and social interaction. Results: As predicted, peripheral oxytocin administration successfully decreased cued heroin seeking on days 1 and 30 of abstinence. Oxytocin administration also led to increased neuronal activity within the PVN and the central amygdala (CeA). Activation of oxytocinergic PVN neurons with an excitatory (Gq) DREADD did not impact cued reinstatement or social interaction. In contrast, suppression with an inhibitory (Gi) DREADD reduced heroin seeking on abstinence day 30 and decreased time spent interacting with a novel conspecific. Discussion: These findings reinforce oxytocin’s therapeutic potential for OUD, the basis for which may be driven in part by increased PVN-CeA circuit activity. Our results also suggest that oxytocin has distinct signaling and/or other mechanisms of action to produce these effects, as inhibition, but not activation, of oxytocinergic PVN neurons did not recapitulate the suppression in heroin seeking.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Paraventricular Nucleus of the Hypothalamus Oxytocin and Incubation of Heroin Seeking

et al. 2023

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“…Low AI males reduced chain pull latency across acquisition, whereas low AI females did not ( Supplemental Figure 1D ). Our lab and others 48-49 use change in latency over time as a proxy for learning and mastery of a behavioral task. While it cannot be ruled out that low AI females showed reduced helping behavior compared to males, it seems less likely since no differences were seen in any of the specific timepoints evaluated.…”

Section: Discussionmentioning

confidence: 99%

Neuronal, Affective, and Sensory Correlates of Targeted Helping Behavior in Male and Female Sprague Dawley Rats

Cox

Brown

Woods

et al. 2022

Preprint

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Empathy is an innate ability to understand the emotional states of others along with the motivation to improve it. It has evolved over time into highly complex behaviors, the basis of which can be described using the Perception Action Model (PAM), where shared affect promotes an action that eliminates the distress of both the passive Target and, by extension, the active Observer. There are myriad biological variables that may modulate empathic behavior, including sex, sensory modalities, and neural activity. In the following studies, using our model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including the impact of direct visualization of a distressed conspecific and the type of ultrasonic vocalizations (USV) made between animal pairs during the task. Finally, we examined the neural activity of multiple cortical and subcortical regions of interest across time during targeted helping between males and females. We show both sexes exhibit similar helping behavior, but sensory and affective signaling differs between sexes. Further, changes in neural activity exhibited distinct sex-specific patterns across time. Our results indicate sex differences are not a ubiquitous presence in targeted helping. Instead, it is likely sex differences may be a convergent phenomenon in which the behavior is similar, but the underlying biological mechanisms are distinct. These results lay the groundwork for future studies to explore the similarities and differences that drive empathic behavior in both males and females.

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“…19 , 20 , 21 , 22 Neuroscience studies in rats have further identified emotional mirror neurons of pain in the ACC 23 and the causal contribution of InC in helping behaviors. 24 Emotional mirror neurons in rats are analogous to the mirror neuron system in primates, which explains their ability to understand observed motor actions. 25 , 26 , 27 …”

Section: Introductionmentioning

confidence: 99%