Serum- and glucocorticoid-inducible kinase 1 activity in ventral tegmental area dopamine neurons regulates cocaine conditioned place preference but not cocaine self-administration

Doyle, Marie; Bali, Vedrana; Eagle, Andrew L.; Stark, Ali; Fallon, Barbara; Neve, Rachael L.; Robison, Alfred J.; Mazei-Robison, Michelle S.

doi:10.1038/s41386-021-01032-3

Cited by 6 publications

(9 citation statements)

References 51 publications

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“…Other compensatory mechanisms independent of CA4 may also come into play. Nonetheless, divergence between CPP and other drug-seeking behaviors including intravenous self-administration is not unprecedented ( 55 , 56 ), and several important behavioral consequences of CA4 disruption were still observed.…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal

et al. 2022

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Cocaine use followed by withdrawal induces synaptic changes in nucleus accumbens (NAc), which are thought to underlie subsequent drug-seeking behaviors and relapse. Previous studies suggest that cocaine-induced synaptic changes depend on acid-sensing ion channels (ASICs). Here, we investigated potential involvement of carbonic anhydrase 4 (CA4), an extracellular pH-buffering enzyme. We examined effects of CA4 in mice on ASIC-mediated synaptic transmission in medium spiny neurons (MSNs) in NAc, as well as on cocaine-induced synaptic changes and behavior. We found that CA4 is expressed in the NAc and present in synaptosomes. Disrupting CA4 either globally, or locally, increased ASIC-mediated synaptic currents in NAc MSNs and protected against cocaine withdrawal–induced changes in synapses and cocaine-seeking behavior. These findings raise the possibility that CA4 might be a previously unidentified therapeutic target for addiction and relapse.

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Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal

et al. 2022

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“…These compounds must then be tested in rodent models, since in silico and cell-based assays cannot definitively determine the behavioral effects of a drug. Cocaine locomotor sensitization in mice can uncover the ability of a compound to block the physiological and psychomotor effects of the drug while cocaine-conditioned place preference can determine whether a compound can prevent a drug reward or drug environment. − Compounds with effects in either of these assays would then be good candidates for testing in the more time-consuming but more rigorous cocaine self-administration model. Examining characteristics like acquisition, breakpoint, extinction, and context- or cue-reinstatement can reveal whether a compound might be useful to block key aspects of cocaine addiction like drug seeking, craving, and relapse. , Of course, compounds that produce promising results in animal testing would then move into further development.…”

Section: Discussionmentioning

confidence: 99%

“…Examining characteristics like acquisition, breakpoint, extinction, and context-or cue-reinstatement can reveal whether a compound might be useful to block key aspects of cocaine addiction like drug seeking, craving, and relapse. 74,76 Of course, compounds that produce promising results in animal testing would then move into further development.…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Analysis of Cocaine Addiction Informed by DAT, SERT, and NET-Based Interactome Networks

Hongsong

Gao

Chen

et al. 2022

J. Chem. Theory Comput.

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Cocaine addiction is a psychosocial disorder induced by the chronic use of cocaine and causes a large number of deaths around the world. Despite decades of effort, no drugs have been approved by the Food and Drug Administration (FDA) for the treatment of cocaine dependence. Cocaine dependence is neurological and involves many interacting proteins in the interactome. Among them, the dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters are three major targets. Each of these targets has a large protein−protein interaction (PPI) network, which must be considered in the anticocaine addiction drug discovery. This work presents DAT, SERT, and NET interactome network-informed machine learning/deep learning (ML/DL) studies of cocaine addiction. We collected and analyzed 61 protein targets out of 460 proteins in the DAT, SERT, and NET PPI networks that have sufficiently large existing inhibitor datasets. Utilizing autoencoder (AE) and other ML/DL algorithms, including gradient boosting decision tree (GBDT) and multitask deep neural network (MT-DNN), we built predictive models for these targets with 115 407 inhibitors to predict drug repurposing potential and possible side effects. We further screened their absorption, distribution, metabolism, and excretion, and toxicity (ADMET) properties to search for leads having potential for developing treatments for cocaine addiction. Our approach offers a new systematic protocol for artificial intelligence (AI)-based anticocaine addiction lead discovery.

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“…For experiment 2, 3% and 7% ethanol solutions were each provided for one week, followed by 4 weeks of 10% ethanol. The following doses were selected based on previous studies indicating altered intake and/or preference across a dose-response curve: Sucrose: 0.5%, 1.0%, and 10% sucrose in tap water (Doyle et al, 2021; Glendinning et al, 2010; Zukerman et al, 2009) Quinine: 0.01g/L, 0.03g/L, and 0.1g/L in tap water (Hodge et al, 1999; Winters et al, 2021) Ethanol: 3%, 7%, and 10% ethanol in tap water (Centanni et al, 2019; Hodge et al, 1999; Winters et al, 2021) …”

Section: Methodsmentioning

confidence: 99%

“…Sucrose: 0.5%, 1.0%, and 10% sucrose in tap water (Doyle et al, 2021; Glendinning et al, 2010; Zukerman et al, 2009)…”

Section: Methodsmentioning

confidence: 99%

LIQ HD (Lick Instance Quantifier Home cage Device): An open-source tool for recording undisturbed two-bottle drinking behavior in a home cage environment

Petersen

Adank

Raghavan

et al. 2022

Preprint

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Investigation of rodent drinking behavior has provided insight into drivers of thirst, circadian rhythms, anhedonia, and drug and ethanol consumption. Traditional methods of recording fluid intake involve periodically weighing bottles, which is cumbersome and lacks temporal resolution. Several open-source devices have been designed to improve drink monitoring, particularly for two-bottle choice tasks. However, recent designs are limited by the use of infrared photobeam-break sensors and incompatibility with prolonged undisturbed use in ventilated home cages. Beam-break sensors lack accuracy for bout microstructure analysis and are prone to damage from rodents. To address these concerns, we designed LIQ HD (Lick Instance Quantifier Home cage Device) with the goal of utilizing capacitive sensors to increase accuracy and analyze lick microstructure, building a device compatible with ventilated vivarium home cages, increasing scale with prolonged undisturbed recordings, and creating a design that is easy to build and use with an intuitive touchscreen graphical user interface. The system tracks two-bottle choice licking behavior in up to 18 rodent home cages, or 36 single bottles, on a minute-to-minute timescale controlled by a single Arduino microcontroller. The data are logged to a single SD card, allowing for efficient downstream analysis. With sucrose, quinine, and ethanol two-bottle choice tasks, we validated that LIQ HD has superior accuracy compared to beam-break sensors. The system measures preference over time and changes in bout microstructure, with undisturbed recordings lasting up to 7 days. All designs and software are open-source to allow other researchers to build upon the system and adapt LIQ HD to their animal home cages.

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Serum- and glucocorticoid-inducible kinase 1 activity in ventral tegmental area dopamine neurons regulates cocaine conditioned place preference but not cocaine self-administration

Cited by 6 publications

References 51 publications

Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal

Carbonic anhydrase 4 disruption decreases synaptic and behavioral adaptations induced by cocaine withdrawal

Machine Learning Analysis of Cocaine Addiction Informed by DAT, SERT, and NET-Based Interactome Networks

LIQ HD (Lick Instance Quantifier Home cage Device): An open-source tool for recording undisturbed two-bottle drinking behavior in a home cage environment

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