Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex

Hynes, Tristan J.; Chernoff, Chloe S.; Hrelja, Kelly M.; Tse, Maric T.L.; Avramidis, Dimitrios K.; Lysenko-Martin, Melanie R.; Calderhead, Lucas; Kaur, Sukhbir; Floresco, Stan B.; Winstanley, Catharine A.

doi:10.1016/j.biopsych.2023.08.021

Cited by 5 publications

(3 citation statements)

References 70 publications

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“…Although we can find no evidence of this in the literature at the time of writing, there have been remarkably few studies published that document the effects of excitatory DREADDs targeted to SNc dopamine neurons. Although we did not directly measure neuronal activity following CNO administration for these experiments, chemogenetic activation of VTA DA neurons using identical methods as reported here is highly efficacious in our hands (Hynes et al, 2024). Nevertheless, we cannot entirely rule out that the chemogenetic approach used here may have not sufficiently activated dopamine neurons in the SNc.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, the same manipulation has the opposite effect in females, increasing risky choice (Hynes et al, 2021). Chemogenetic activation of the VTA also results in diametrically opposing effects across sexes, with males developing a preference for the risky options more rapidly and females more slowly (Hynes et al, 2024). Dopamine activity in the dorsal striatum, innervated by the substantia nigra pars compacta (SNc), has not yet been investigated on this task and may contribute to the development of choice patterns.…”

Section: Introductionmentioning

confidence: 99%

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Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats

Hathaway,

Li,

Brodie

et al. 2024

Eur J of Neuroscience

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Deficits in cost/benefit decision making is a critical risk factor for gambling disorder. Reward‐paired cues may play an important role, as these stimuli can enhance risk preference in rats. Despite extensive research implicating the dorsal striatum in the compulsive aspects of addiction, the role of nigrostriatal dopaminergic activity in cue‐induced risk preference remains unclear, particularly in females. Accordingly, we examined the effects of manipulating the dopaminergic nigrostriatal pathway on cue‐induced risky choice in female rats. TH:Cre rats were trained on the cued version of the rat Gambling Task. This task was designed such that maximal reward is attained by avoiding the high‐risk, high‐reward options and instead favouring the options associated with lower per‐trial gains, as they feature less frequent and shorter time‐out penalties. Adding reward‐paired audiovisual cues to the task leads to greater risky choice on average. To assess the role of the nigrostriatal pathway, a viral vector carrying either Cre‐dependent inhibitory or excitatory DREADD was infused into the substantia nigra. Rats then received clozapine‐N‐oxide either during task acquisition or after a stable performance baseline was reached. Inhibition of this pathway accelerated the development of risk preference in early sessions and increased risky choice during performance, but long‐term inhibition actually improved decision making. Activation of this pathway had minimal effects. These results provide evidence for the involvement of the dopaminergic nigrostriatal pathway in cue‐induced risk preference in females, therefore shedding light on its role in cost/benefit decision‐making deficits and expanding our knowledge of the female dopaminergic system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats

Hathaway,

Li,

Brodie

et al. 2024

Eur J of Neuroscience

Self Cite

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“…In human adolescents, both of these factors – male sex and older age – are positively associated with problem gambling ( Dowling et al, 2017 ; Richard and King, 2023 ), and human young adult males are more likely than females to show signs of GD ( Wong et al, 2013 ). However, in adult rats, studies have found that sex differences in performance on the rGT are absent or subtle at baseline, depending on the specific analysis ( Georgiou et al, 2018 ; Hynes et al, 2020 ), although male and female rats vary in their response to dopaminergic manipulations during this task ( Hynes et al, 2021 , 2023 ). Further research is needed to examine possible sex differences among adolescents in risky decision-making during the rGT.…”

Section: Discussionmentioning

confidence: 99%

Propensity for risky choices despite lower cue reactivity in adolescent rats

Zeng,

McLaughlin,

Ramesh

et al. 2023

Front. Behav. Neurosci.

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Adolescence is a time of heightened risk-taking across species. Salient audiovisual cues associated with rewards are a common feature of gambling environments and have been connected to increased risky decision-making. We have previously shown that, in adult male rats, sign tracking – a behavioral measure of cue reactivity – predicts an individual’s propensity for suboptimal risky choices in a rodent gambling task (rGT) with win-paired cues. However, adolescents perform less sign tracking than adult animals, suggesting that they are less cue-reactive than adults in some circumstances. Therefore, we investigated the performance of adolescent male rats on the rGT with win cues and examined its relationship with their sign-tracking behavior. We found that adolescents make more risky choices and fewer optimal choices on the rGT compared with adults, evidence of the validity of the rGT as a model of adolescent gambling behavior. We also confirmed that adolescents perform less sign tracking than adults, and we found that, unlike in adults, adolescents’ sign tracking was unrelated to their risk-taking in the rGT. This implies that adolescent risk-taking is less likely than that of adults to be driven by reward-related cues. Finally, we found that adults trained on the rGT as adolescents retained an adolescent-like propensity toward risky choices, suggesting that early exposure to a gambling environment may have a long-lasting impact on risk-taking behavior.

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Increased risky choice during forced abstinence from fentanyl on the cued rat gambling task

Hrelja,

Kawkab,

Avramidis

et al. 2024

Psychopharmacology

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Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex

Cited by 5 publications

References 70 publications

Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats

Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats

Propensity for risky choices despite lower cue reactivity in adolescent rats

Increased risky choice during forced abstinence from fentanyl on the cued rat gambling task

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