Mesolimbic dopamine release precedes actively sought aversive stimuli in mice

Abstract

In some models, animals approach aversive stimuli more than those housed in an enriched environment. Here, we found that male mice in an impoverished and unstimulating (i.e., boring) chamber without toys sought aversive air puffs more often than those in an enriched chamber. Using this animal model, we identified the insular cortex as a regulator of aversion-seeking behavior. Activation and inhibition of the insular cortex increased and decreased the frequencies of air-puff self-stimulation, respectively, and the firing patterns of insular neuron ensembles predicted the self-stimulation timing. Dopamine levels in the ventrolateral striatum decreased with passive air puffs but increased with actively sought puffs. Around 20% of mice developed intense self-stimulation despite being offered toys, which was prevented by administering opioid receptor antagonists. This study establishes a basis for comprehending the neural underpinnings of usually avoided stimulus-seeking behaviors.

Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?

“…Along this line, a preclinical study found that memories of previous intestinal inflammations (induced in rodents by mixing dextran sodium sulfate (DSS) with drinking water) are stored in IC, and stimulation of this area, weeks or months later, can trigger intestinal inflammation in the absence of DSS [62,118]. This study is in line with other research data on interoceptive awareness and IC, likely pinpointing the neuroanatomical location of an "insight center" [64,118,119]. Indeed, functional neuroimaging and connectivity studies have demonstrated that the awareness of error, insight, and the position of limbs is regulated by the IC neuronal networks [120].…”

“…For example, upregulated plasma levels of immunoglobulins M and/or A against Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Pseudomonas putida, and Klebsiella pneumoniae were found in SCZ patients with negative symptoms, further linking this disorder to microbial translocation [12]. Furthermore, poor insight or anosognosia, a characteristic SCZ feature, present in up to 98% of patients, was associated with intestinal-inflammation-induced IC pathology [62][63][64][65].…”

Homeostatic Control on the Thought: a Comprehensive Explanation of Mind Wandering

“…Taken together, there can be a similar principle behind human thoughts and transitions between them to those of animal behaviors. Boredom-like behavior in which animals and humans tend to accept aversive stimulus, such as electric shocks or air puffs, in a poor environment, and its neural substrates support our idea (Wilson et al, 2014;Yawata et al, 2023). When the environment is poor, agent homeostatic states for available actions should satiate, and aversive stimulus should become a reward by reducing satiation.…”

“…The insular cortex, which constitutes the SN, is known to be involved with emotional and physical responses (Schimmelpfennig et al, 2023). This region is also activated immediately before action selection changes, especially in environments with little change (Munn et al, 2021;Yawata et al, 2023). Our simulations revealed that the transitions from task engagement to TUT and from TUT to task engagement are driven by saturation of the currently engaged action (Fig.…”

“…When the environment is poor, agent homeostatic states for available actions should satiate, and aversive stimulus should become a reward by reducing satiation. In such a situation, the insular cortex, a part of SN, was involved in the boredom-like behavior, and mesolimbic dopaminergic neurons were excited around the aversive stimulus presentations (Yawata et al, 2023). We showed that "TUT" reduced the saturation of the homeostatic state for "focus," and it works as a reward for "TUT" (Fig.…”