Restoration of prosocial behavior in rats after heroin self-administration via chemogenetic activation of the anterior insular cortex

Tomek, Seven E.; Stegmann, Gabriela; Leyrer‐Jackson, Jonna M.; Pina, José Antonio López

doi:10.1080/17470919.2020.1746394

Cited by 14 publications

(7 citation statements)

References 36 publications

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“…The anterior insula (AI) has been implicated as a critical neural substrate for numerous prosocial behaviors in both rodents 31 – 33 and humans 34 – 38 , potentially making it a translationally relevant region controlling empathic behavior. However, until now it was unknown if the role of the AI in rats was related to the rewarding effects of social contact or the process of aiding a conspecific.…”

Section: Discussionmentioning

confidence: 99%

“…In animal studies, the insula has been implicated in social approach and avoidance behaviors under certain social contexts 31 . Further, inactivation of the insula reverses hyperalgesia induced by emotional contagion of pain 32 , while chemogenetic activation of the AI restores a heroin-induced decrease in targeted helping 33 . These data seem to strongly correlate to clinical findings, as functional neuroimaging studies demonstrate an overlapping activity pattern in the AI when directly receiving, or vicariously viewing another receive a painful stimulus 34 – 36 .…”

Section: Introductionmentioning

confidence: 99%

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

Cox

Kearns

Woods

et al. 2022

Sci Rep

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Empathy, the understanding of the emotional state of others, can be examined across species using the Perception Action Model, where shared affect promotes an action by “Observers” to aid a distressed “Target”. The anterior insula (AI) has garnered interest in empathic behavior due to its role integrating sensory and emotional information of self and other. In the following studies, the AI was inhibited pharmacologically and chemogenetically during targeted helping. We demonstrate the insula is active during, and is necessary for the maintenance of, targeted helping. Analysis of ultrasonic vocalizations revealed distress calls from Targets increased when Observers’ helping was attenuated due to insula inhibition. Targets’ elevated distress was directly correlated to Observers’ diminished helping behavior, suggesting emotional transfer between Observer and Target is blunted following Observer AI inhibition. Finally, the AI may selectively blunt targeted helping, as social exploration did not change in a social reward place conditioning task. These studies help further establish the anterior insula as a critical node in the empathic brain during targeted helping, even in the absence of direct social contact.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cox

Kearns

Woods

et al. 2022

Sci Rep

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“…A/N ratios were calculated by measuring the peak amplitude of each current and taking a ratio. For DREADD function validation, see procedures outlined in (Tomek, Stegmann et al 2020). All recordings were conducted using the recording software Axograph.…”

Section: Electrophysiologymentioning

confidence: 99%

Accumbens Cholinergic Interneurons Mediate Cue-Induced Nicotine Seeking and Associated Glutamatergic Plasticity

Leyrer‐Jackson

Holter

Overby

et al. 2020

eNeuro

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Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs) which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes is unknown. ChIs represent less than 1% of the accumbens neuronal population and are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine seeking behavior. Using chemogenetics in transgenic rats expressing Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bi-directionally manipulated prior to cueinduced reinstatement. Following nicotine self-administration and extinction, ChIs were activated or inhibited prior to a cue reinstatement session. Following reinstatement, whole-cell electrophysiology from NAcore MSNs was used to assess changes in plasticity, measured via α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid (AMPA) / N-Methyl-D-Aspartate (NMDA) (A/N) ratios. Chemogenetic inhibition of ChIs inhibited cued nicotine seeking and resulted in decreased A/N, relative to control animals, whereas activation of ChIs was unaltered, demonstrating that ChI inhibition may modulate plasticity underlying cue-induced nicotine seeking. These results demonstrate that ChI neurons play an important role in mediating cue-induced nicotine reinstatement and underlying synaptic plasticity within the NAcore.

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“…A/N ratios were calculated by measuring the peak amplitude of each current and taking a ratio. For DREADD function validation, see procedures outlined in [34].…”

Section: Whole-cell Electrophysiologymentioning

confidence: 99%

Accumbens cholinergic interneurons mediate cue-induced nicotine seeking and associated glutamatergic plasticity

Leyrer‐Jackson

Holter

Overby

et al. 2020

Preprint

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Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs) which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes in unknown. ChIs represent less than 1% of the accumbens neuronal population yet are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine seeking behavior. Using chemogenetics transgenic rats that express Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bi-directionally manipulated prior to cueinduced reinstatement. Following nicotine self-administration and extinction training, ChIs were activated or inhibited prior to a cue reinstatement session. Following reinstatement, whole-cell electrophysiology from NAcore MSNs was used to assess changes in plasticity, measured via α amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) / N-Methyl-D-Aspartate (NMDA) (A/N) ratios. Chemogenetic inhibition of ChIs inhibited cued nicotine seeking and resulted in decreased A/N, whereas activation of ChIs had no effect, demonstrating that ChI inhibition prevents transient synaptic potentiation (t-SP) associated with cue-induced nicotine seeking. To assess potential underlying mechanisms, accumbens α 4 β 2 -and α 7 -containing nicotinic ACh receptors (nAChRs) were pharmacologically inhibited and MSN synaptic morphology was assessed following reinstatement.Inhibition of both nAChR subtypes prevented cue-induced nicotine seeking and t-SP (measured via changes in spine head diameter). Together, these results demonstrate that these neurons mediate cue-induced nicotine reinstatement and underlying synaptic plasticity within the NAcore.--250 words--3 Introduction:

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Restoration of prosocial behavior in rats after heroin self-administration via chemogenetic activation of the anterior insular cortex

Cited by 14 publications

References 36 publications

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

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

Accumbens Cholinergic Interneurons Mediate Cue-Induced Nicotine Seeking and Associated Glutamatergic Plasticity

Accumbens cholinergic interneurons mediate cue-induced nicotine seeking and associated glutamatergic plasticity

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