Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity
| Autor: | Sukhbir Kaur, Lawrence Ma, Brett A. Hathaway, Sophie A. Ebsary, Brittney Russell, Graeme D Betts, Catharine A. Winstanley, Tristan J Hynes, Celine D Hounjet, Chloe S. Chernoff, Kelly M. Hrelja |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Tyrosine 3-Monooxygenase Neural substrate media_common.quotation_subject Decision Making Medicine (miscellaneous) Cre recombinase Self Administration Biology Impulsivity Inhibitory postsynaptic potential Animals Genetically Modified 03 medical and health sciences Cocaine-Related Disorders 0302 clinical medicine Sex Factors Dopamine medicine Animals media_common Pharmacology Tyrosine hydroxylase Behavior Animal Integrases Addiction Dopaminergic Neurons Ventral Tegmental Area 030227 psychiatry Rats Ventral tegmental area Psychiatry and Mental health medicine.anatomical_structure Gambling Impulsive Behavior Female medicine.symptom Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Addiction biologyREFERENCES. 26(6) |
| ISSN: | 1369-1600 |
| Popis: | Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may like-wise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward-paired cues, and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5-hSyn-DIO-hM4D(Gi)-mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self-administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes, therefore we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue-induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine-induced deficits in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction-relevant behaviours, depending on biological sex and dependent variable of interest. |
| Databáze: | OpenAIRE |
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