A Procedure to Study Stress-Induced Relapse of Heroin Seeking after Punishment-Imposed Abstinence

Borges, Catarina S. P.; Charles, Jordan; Shalev, Uri

doi:10.3791/63657

Cited by 2 publications

(2 citation statements)

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“…In our experiments, conditioning with opioid drugs (morphine or fentanyl) led to the formation of contextual reward memory and subsequent risk-taking behavior. These results resemble those from prior rodent studies using opioid self-administration punished by electrical footshocks, which reported near complete suppression of opioid seeking as a function of footshock intensity [6,7,10–15,19]. However, similar studies have reported either incomplete suppression of opioid seeking or divergent behavioral responses that resulted in subgroups of either punishment-sensitive or punishment-resistant animals [8,9].…”

Section: Discussionsupporting

confidence: 84%

“…To investigate potential causality between opioid use and increased risky decision making, prior studies have attempted to model risky opioid use in laboratory animals. Results have shown that rodents will continue to seek opioids even when they must risk the threat of painful stimuli (e.g., electrical footshocks) to do so [6][7][8][9][10][11][12][13]. Other studies have made further attempts to model the use of opioids in a risky context by introducing an electrified barrier that animals had to cross to obtain the drug [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Quave,

Vasquez,

Aquino-Miranda

et al. 2024

Preprint

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Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed a novel approach-avoidance conflict model using a modified conditioned place preference paradigm to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision making. Upon establishment of morphine conditioned place preference, rats underwent a subsequent conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline control group avoided the cat odor side, the morphine group maintained preference for the paired side despite the presence of cat odor. K-means clustering identified two subsets of morphine-treated rats that exhibited either persistent drug seeking (Risk-Takers) or increased avoidance (Risk-Avoiders) during conflict. Single-unit recordings from the prelimbic cortex (PL) revealed decreased neuronal firing rates upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, while this inhibitory signal was lost during the subsequent conflict test in both saline and Risk-Avoider groups, these inhibitory responses persisted in Risk-Takers. Our results suggest that loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, persistent PL inhibitory signaling in the drug associated context during conflict may underlie increased risk taking following opioid exposure.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Quave,

Vasquez,

Aquino-Miranda

et al. 2024

Preprint

View full text Add to dashboard Cite

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Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment

Li,

McCloskey,

Inan

et al. 2024

Neuropsychopharmacol.

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One hallmark of substance use disorder is continued drug use despite negative consequences. When drug-taking behavior is punished with aversive stimuli, i.e. footshock, rats can also be categorized into punishment-resistant or compulsive vs. punishment-sensitive or non-compulsive phenotypes. The serotonin (5-hydroxytryptamine, 5-HT) system modulates responses to both reward and punishment. The goal of the current study was to examine punishment phenotypes in heroin self-administration and to determine the role of dorsal raphe nucleus (DRN) 5-HT neurons in both basal and punished heroin self-administration. First, rats were exposed to punished heroin self-administration and neuronal excitability of DRN 5-HT neurons was compared between punishment-resistant and punishment-sensitive phenotypes using ex vivo electrophysiology. Second, DRN 5-HT neuronal activity was manipulated in vivo during basal and punished heroin self-administration using chemogenetic tools in a Tph2-iCre rat line. While rats separated into punishment-resistant and punishment-sensitive phenotypes for punished heroin self-administration, DRN 5-HT neuronal excitability did not differ between the phenotypes. While chemogenetic inhibition of DRN 5-HT neurons was without effect, chemogenetic activation of DRN 5-HT neurons increased both basal and punished heroin self-administration selectively in punishment-resistant animals. Additionally, the responsiveness to chemogenetic activation of DRN 5-HT neurons in basal self-administration and motivation for heroin in progressive ratio each predicted resistance to punishment. Therefore, our data support the role for the DRN 5-HT system in compulsive heroin self-administration.

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A Procedure to Study Stress-Induced Relapse of Heroin Seeking after Punishment-Imposed Abstinence

Cited by 2 publications

References 0 publications

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Neural signatures of opioid-induced risk-taking behavior in the prelimbic prefrontal cortex

Role of serotonin neurons in the dorsal raphe nucleus in heroin self-administration and punishment

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