Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice

Jing, Manyi; Ding, Xiaoyan; Han, Xiao; Zhao, Tai-Yun; Luo, Minmin; Wu, Ning; Li, Jin; Song, Rui

doi:10.1038/s41401-022-00866-x

Cited by 8 publications

(2 citation statements)

References 56 publications

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“…We believe the three distinct groups we see mimic real-world variability in initial interactions with drugs of abuse. Future research should investigate the neurobiological mechanisms underlying our task, particularly focusing on connectivity between the insula, medial prefrontal cortex, and ventral striatum which are implicated in aversive-resistant motivation and drug/reward-seeking (Peciña and Berridge, 2005; Hurley and Carelli, 2020; Naqvi et al, 2007; Moorman and Aston-Jones, 2015; Moschak et al, 2018; Jing et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine

Powers,

Fogel,

Reeves

et al. 2024

Preprint

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BackgroundOnly a subset of individuals who encounter drugs of abuse become habitual users. Aversive subjective effects like coughing and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop a clinically relevant model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigating whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions.MethodsTwenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2 hr/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR).ResultsWe identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who “overindulge” on their first use and subsequently find self-administration to be aversive.ConclusionsOur novel model mimics real-world variability in initial interactions with drugs of abuse and yields three distinct groups that differ in self-administration patterns and aversive cue valuation.

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Section: Discussionmentioning

confidence: 99%

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine

Powers,

Fogel,

Reeves

et al. 2024

Preprint

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“…In our present study, we found that arecoline significantly enhanced the firing rates and burst activities of VTA dopaminergic neurons, but exerted no significant effects on GABA neuronal firings, which was similar to the effects of cocaine on the firing characteristics of the dopaminergic and GABAergic neurons ( Creed et al, 2016 ). Increased dopaminergic neuron activities will enhance extrasynaptic dopamine levels, and the burst firings in particular markedly promote synaptic dopamine release ( Floresco et al, 2003 ), which is strongly associated with substance dependence ( Zhang et al, 2018 ; Jing et al, 2022 ). Therefore, arecoline-induced VTA dopamine neuron excitation may, to some extent, associate with the addictive phenotypes of areca nut users.…”

Section: Discussionmentioning

confidence: 99%

Arecoline Induces an Excitatory Response in Ventral Tegmental Area Dopaminergic Neurons in Anesthetized Rats

et al. 2022

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Arecoline is the principle psychoactive alkaloid in areca nuts. Areca nuts are chewable seeds of Areca catechu L., which are epidemic plants that grow in tropical and subtropical countries and cause dependency after long-term use. However, the mechanisms underlying such dependency remain largely unclear, and therefore, no effective interventions for its cessation have been developed. The present study aimed to examine the effects of arecoline on neurons of the ventral tegmental area (VTA). After rats were anesthetized and craniotomized, electrophysiological electrodes were lowered into the VTA to obtain extracellular recordings. The mean firing rate of dopaminergic and GABAergic neurons were then calculated and analyzed before and after arecoline treatment. The burst characteristics of the dopaminergic neurons were also analyzed. The results showed that arecoline evoked a significant enhancement of the firing rate of dopaminergic neurons, but not GABAergic neurons. Moreover, arecoline evoked remarkable burst firings in the dopaminergic neurons, including an increase in the burst rate, elongation in the burst duration, and an enhancement in the number of spikes per burst. Collectively, the findings revealed that arecoline significantly excited VTA dopaminergic neurons, which may be a mechanism underlying areca nut dependency and a potential target for areca nut cessation therapy.

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Impacts of dopamine on learning and behavior in health and disease: Insights from optogenetics in rodents

Campbell,

Green,

Romero Pinto

et al. 2025

Encyclopedia of the Human Brain

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Activation of mesocorticolimbic dopamine projections initiates cue-induced reinstatement of reward seeking in mice

Cited by 8 publications

References 56 publications

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine

Distinct populations suppress or escalate intake of cocaine paired with aversive quinine

Arecoline Induces an Excitatory Response in Ventral Tegmental Area Dopaminergic Neurons in Anesthetized Rats

Impacts of dopamine on learning and behavior in health and disease: Insights from optogenetics in rodents

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