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Nova · Professor Researcher · re-ranking top 20…

Gary Aston-Jones

· Distinguished Professor

Rutgers University · Psychiatry

Active 1980–2025

h-index116
Citations57.5k
Papers37636 last 5y
Funding
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About

Gary Aston-Jones is a faculty member associated with the Rutgers Brain Health Institute, which is part of Rutgers University. The institute hosts over 300 laboratories across 50 departments and 14 schools, emphasizing a broad and collaborative approach to neuroscience research. While the specific research focus of Dr. Aston-Jones is not detailed in the provided text, the institute's activities include hosting seminars, symposiums, and funding opportunities related to brain science, cognitive neuroscience, and mental health. The institute aims to advance neuroscience through research, education, and community engagement, fostering collaborations among researchers, clinicians, and supporters to revolutionize brain health.

Selected publications

  • Floyd E. Bloom (1936–2025)

    Nature Neuroscience · 2025-02-25

    editorialOpen access1st authorCorresponding
  • Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use

    Molecular Psychiatry · 2025-01-29 · 3 citations

    articleOpen access

    The hypothalamic neuropeptide system of orexin (hypocretin) neurons provides projections throughout the neuraxis and has been linked to sleep regulation, feeding and motivation for salient rewards including drugs of abuse. However, relatively little has been done to examine genes associated with orexin signaling and specific behavioral phenotypes in humans. Here, we tested for association of twenty-seven genes involved in orexin signaling with behavioral phenotypes in humans. We tested the full gene set, functional subsets, and individual genes involved in orexin signaling. Our primary phenotype of interest was Externalizing, a composite factor comprised of behaviors and disorders associated with reward-seeking, motivation, and behavioral regulation. We also tested for association with additional phenotypes that have been related to orexin regulation in model organism studies, including alcohol consumption, problematic alcohol use, daytime sleepiness, insomnia, cigarettes per day, smoking initiation, and body mass index. The composite set of 27 genes corresponding to orexin function was highly associated with Externalizing, as well as with alcohol consumption, insomnia, cigarettes per day, smoking initiation and BMI. In addition, all gene subsets (except the OXR2/HCRTR2 subset) were associated with Externalizing. BMI was significantly associated with all gene subsets. The "validated factors for PPOX/HCRT" and "PPOX/HCRT upregulation" gene subsets also were associated with alcohol consumption. Individually, 8 genes showed a strong association with Externalizing, 12 with BMI, 7 with smoking initiation, 3 with alcohol consumption, and 2 with problematic alcohol use, after correction for multiple testing. This study indicates that orexin genes are associated with multiple behaviors and disorders related to self-regulation in humans. This is consistent with prior work in animals that implicated orexin signaling in motivational activation induced by salient stimuli, and supports the hypothesis that orexin signaling is an important potential therapeutic target for numerous behavioral disorders.

  • IN MEMORIAM: Floyd E. Bloom, M.D

    Neuropsychopharmacology · 2025-03-05

    editorialOpen access1st authorCorresponding
  • A founding father of neuroscience: Floyd E. Bloom, 1936–2025

    Proceedings of the National Academy of Sciences · 2025-05-15

    articleOpen access1st authorCorresponding

    Floyd E. Bloom, M.D. was a prominent leader and spokesperson for the neuroscience and broader scientific communities; sadly, Floyd passed away on January 8, 2025. His scientific contributions were focused on multidisciplinary characterizations of transmitter-specific neural pathways in the brain. An innovative neuroanatomist and neurophysiologist, he spearheaded the development of new techniques and multidisciplinary paradigms for demonstrating the functions of neurotransmitters at the circuit, cellular, and subcellular levels. His work was especially important for mapping monoaminergic and peptidergic pathways and describing their physiologic and behavioral roles. He played a seminal role in developing the field of modern neuropharmacology at all levels, from the molecular to the behavioral.

  • Augmented orexin/hypocretin signaling underlies negative affect during acute oxycodone abstinence in rats.

    Research Square · 2025-10-13

    preprintOpen access1st authorCorresponding
  • Oxytocin attenuates demand for cocaine in female rats

    Addiction Neuroscience · 2025-01-15 · 1 citations

    articleOpen accessSenior author

    There are substantial sex differences in substance use disorders (SUDs), and a key feature of SUD is pathologically high economic demand for drug. The hypothalamic neuropeptide oxytocin (OXT) is heavily implicated in the modern treatment of SUDs. Using a within-session threshold behavioral economics (BE) procedure, we quantified demand elasticity (a, inverse motivation) and free consumption (Q 0 ) in male and female rats to investigate the effect of OXT on cocaine demand. Results showed that OXT decreased motivation for cocaine; an effect greater during the high-demand phase (diestrus, low progesterone, P 4 ) vs low demand phases (proestrus, high P 4 ). We confirmed our prior findings that P 4 attenuates cocaine demand in female rats and that chronic cocaine self-administration disrupts estrus cyclicity. Following each injection, OXT at either 0.1mg/kg or 0.3mg/kg restored estrous cycling in intact females with prior cocaine experience for one week and remained effective with up to 4 weeks of injections. Fos reactivity in OXT+ neurons was greater when rats were in proestrus compared to diestrus and significantly correlated to motivation and circulating levels of P 4 . Finally, using ovariectomized females with P 4 replacement, we show that P 4 ’s demand attenuating effects are reversed by atosiban (1.0 mg/kg, IP), an OXT antagonist. These data show an interaction between oxytocin and progesterone in female rats that may underlie differences in cocaine demand between sexes. Additionally, we show critical periods for using OXT as a treatment to reduce cocaine demand in females. Our results indicate novel therapeutic treatments for SUDs must be tailored to hormonal states.

  • Serotonin signaling in hippocampus during initial cocaine abstinence drives persistent drug seeking

    Journal of Neuroscience · 2024-03-21 · 3 citations

    articleOpen accessSenior author

    The initiation of abstinence after chronic drug self-administration is a stressful event. Cocaine-seeking behavior on the first day of the absence of expected drug (extinction day 1, ED1) is reduced by blocking 5-HT signaling in dorsal hippocampus CA1 (CA1) in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior, and that dorsal raphe serotonin (DR 5-HT) input to CA1 may be involved. We inhibited 5-HT1A/1B receptors (WAY100,635 plus GR127935), or DR input (chemogenetics), in CA1 on ED1 to test the role of this pathway on cocaine-seeking persistence 2wk later. We also inhibited 5-HT1A or 5-HT1B receptors in CA1 during conditioned place preference (CPP) for cocaine, to examine mechanisms involved in persistent effects of ED1 manipulations. Inhibition of DR inputs, or 5-HT1A/1B signaling, in CA1 decreased drug-seeking on ED1 and decreased cocaine-seeking 2wk later revealing that 5-HT signaling in CA1 during ED1 contributes to persistent drug-seeking during abstinence. In addition, 5-HT1B antagonism alone transiently decreased drug-associated memory performance when given prior to a conditioned place preference (CPP) test, whereas similar antagonism of 5-HT1A alone had no such effect but blocked CPP retrieval on a test 24h later. These CPP findings are consistent with prior work showing that DR inputs to CA1 augments recall of the drug-associated context and drug-seeking via 5-HT1B receptors and prevents consolidation of the updated non-drug context via 5-HT1A receptors. Thus, treatments that modulate 5-HT dependent memory mechanisms in CA1 during initial abstinence may facilitate later maintenance of abstinence. Significance Statement One of the most complex issues associated with substance use disorder (SUD) treatment is the development of strategies that assist in the initiation and maintenance of abstinence from drug taking. Herein, we show that the persistent propensity for cocaine-seeking during abstinence can be attenuated by 5-HT1A/5-HT1B receptor antagonists, or by inhibition of dorsal raphe signaling to dorsal hippocampus. Our results provide insight towards potential clinical applications for treatment of addiction in human populations.

  • Orexins in Food and Addiction

    2024-09-19

    book-chapterSenior author

    Abstract This chapter introduces the hypothalamic orexin (hypocretin) neuropeptide system as a common brain system underlying seeking and craving of foods and drugs of abuse. The orexin system is readily engaged by both palatable foods and drugs of abuse, as well as by stimuli that predict their availability. Orexin release, in turn, engages downstream reward structures to promote motivated food- or drug-directed behaviors. Chronic exposure to food or drugs results in increased numbers and excitability of orexin-expressing neurons, and compounds that block orexin signaling (particularly at the orexin-1 receptor) are effective at reducing food and drug behaviors. Here, we provide an up-to-date overview of this evidence, which together points to the potential utility of orexin-based compounds for the management of “addiction” to both drugs of abuse and certain foods.

  • In search of the locus coeruleus: guidelines to identify anatomical boundaries and physiological properties of the blue spot in mice, fish, finches and beyond

    Journal of Neurophysiology · 2024-06-06 · 7 citations

    reviewOpen access

    Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of correctly identifying analogous structures as research efforts expand to other vertebrates, we suggest adoption of consensus anatomical and electrophysiological guidelines for identifying LC neurons across species when evaluating brainstem single-unit spiking or calcium imaging. Such consensus criteria will allow for confident cross-species understanding of the roles of the LC in brain function and behavior.

  • Fentanyl demand and seeking in female rats: Role of the orexin system and estrous cycle

    Addiction Neuroscience · 2024-10-09 · 1 citations

    articleOpen accessSenior authorCorresponding

    • The orexin 1 receptor antagonist SB-334867 has no effect on fentanyl demand in females • SB-334867 decreases cued reinstatement of fentanyl seeking in females • Proestrus increases fentanyl demand in naïve subjects, but decreases demand in subjects after chronic fentanyl self-administration. • Fentanyl intake disrupts the estrous cycle The orexin system plays a major role in drug reward. Orexin-1 receptor (OxR1) blockade reduces fentanyl demand in males. However, there are a number of sex differences in the orexin system, and it is unclear how OxR1 antagonism would decrease fentanyl demand in females. Furthermore, the relationships between the estrous cycle and fentanyl intake are yet to be delineated. Here, we conducted a behavioral economics (BE) procedure in female rats to assess the effects of the OxR1 antagonist SB-334867 on fentanyl demand before and after short-(ShA), long- (LgA) or intermittent-access (IntA) self-administration of fentanyl; we also tested the effect of SB-334867 on cued reinstatement of fentanyl seeking. Finally, we measured the impact of the estrous cycle on fentanyl demand, intake and seeking. Results showed that in females SB-334867 did not consistently modulate demand for fentanyl before or after chronic access periods. However, SB-334867 at 30mg/kg reduced the number of active lever presses during cued-reinstatement of fentanyl seeking. We also found that fentanyl self-administration disrupted estrous cyclicity, in particular proestrus epochs, an effect that depended on short versus chronic access. Furthermore, extended access to fentanyl shifted the role of progesterone from facilitation of fentanyl demand during short periods, to attenuation of fentanyl demand after long term exposure. These results indicate that an orexin-based therapy in women for treating opioid use disorder must consider prior drug history as well as cycle phase.

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