Kenner C Rice

Kenner C Rice
National Institutes of Health | NIH · National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Doctor of Philosophy

About

1,136
Publications
93,094
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43,595
Citations
Citations since 2016
164 Research Items
12117 Citations
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201620172018201920202021202205001,0001,5002,000

Publications

Publications (1,136)
Article
Major depressive disorder (MDD) is a debilitating disease with a high worldwide prevalence. Despite its greater prevalence in women, male animals are used in most preclinical studies of depression even though there are many sex differences in key components of depression, such as stress responses and immune system functions. In the present study, w...
Article
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Up to 92% of patients suffering from multiple sclerosis (MS) experience pain, most without adequate treatment, and many report pain long before motor symptoms associated with MS diagnosis. In the most commonly studied rodent model of MS, experimental autoimmune encephalomyelitis (EAE), motor impairments/disabilities caused by EAE can interfere with...
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The quantitation of the available antibody binding-site concentration of polyclonal antibodies in serum is critical in defining the efficacy of vaccines against substances of abuse. We have conceptualized an equilibrium dialysis (ED)-based approach coupled with fluorimetry (ED-fluorimetry) to measure the antibody binding-site concentration to the l...
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Rationale Ayahuasca has been proposed as a potential treatment of alcohol (ethanol) use disorder (AUD). The serotonin 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) is the main psychoactive component of ayahuasca, suggesting that its therapeutic effects may be mediated by 5-HT2A receptors. Objectives The aim of the present study was to inves...
Article
Two modifications of previous procedures enabled the high-yield scalable synthesis of the pharmacologically important enantiomers of a C9-keto-5-phenylmorphan ((1R,5R)- and (1S,5S)-5-(3-methoxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-9-one). The use of sodium hydride rather than sodium amide as the base improved yields in two of the 6 step synthes...
Article
Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are recreational drugs of abuse often identified in 'bath salts' preparations. Humans report compulsive patterns of bath salts use, and previous work suggests that a subset of rats develop unusually high levels of MDPV self-administration. This study aims to test the hypothesis th...
Article
It is becoming increasingly clear among treatment providers, policy makers, and basic scientists alike, that polysubstance abuse is the norm rather than the exception. This is supported by the increased incidence of drug mixtures in drug overdoses, both fatal and nonfatal. In particular, toxicity produced via use of multiple substances has been hig...
Conference Paper
A subset of rats that self-administer synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), develop high levels of drug intake and patterns of responding similar to the compulsive, binge-like patterns of cathinone (e.g., "bath salts") use reported in humans. Though high-responder rats exhibit some behaviors thought to be related to s...
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This paper shows that repeated exposure (3x daily until completing 19 administrations) to morphine and fentanyl produces tolerance to their antinociceptive effects. Fentanyl also causes hyperalgesia. Using this administration schedule, both opioids produce neuroinflammation, NLRP3 activation and pyroptosis in serotonergic neurons in the dorsal raph...
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In our continuing effort to develop effective anti-heroin vaccines as potential medications for the treatment of opioid use disorder, herein we present the design and synthesis of the haptens: 1-AmidoMorHap (1), 1-AmidoMorHap epimer (2), 1 Amido-DihydroMorHap (3), and 1 Amido-DihydroMorHap epimer (4). This is the first report of hydrolytically stab...
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Background Recent evidence suggesting that polysubstance use is the norm rather than the exception highlights the need for a better understanding of interactions amongst the abuse-related effects of commonly co-abused drugs. Synthetic cathinones remain one of the most popular families of novel psychoactive substances and are typically used in prepa...
Conference Paper
Prolonged cognitive deficits following surgery are associated with higher risk for mortality and dementia in the elderly. Mechanisms driving susceptibility for these persistent deficits are not well understood. Even less is understood about how post-operative opioids impact post-surgical cognition. Here we report that treatment with post-surgical m...
Conference Paper
Background: POCD is a surgical complication characterized by confusion, executive function deficits & memory impairment. Persistent POCD is experienced by some older individuals & is associated with increased risk of dementia. We've shown that morphine treatment exaggerates & prolongs surgery-induced inflammation, leading to persistent POCD lasting...
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The prevalence and societal impact of opioid use disorder (OUD) is an acknowledged public health crisis that is further aggravated by the current pandemic. One of the devastating consequences of OUD is opioid overdose deaths. While multiple medications are now available to treat OUD, given the prevalence and societal burden, additional well-tolerat...
Article
Rationale: Exposure to a drug can subsequently impact its own reactivity as well as that of other drugs. Given that users of synthetic cathinones, i.e., “bath salts”, typically have extensive and varied drug histories, an understanding of the effects of drug history on the behavioral and physiological consequences of synthetic cathiones may be impo...
Article
Preclinical and human studies have indicated involvement of the ghrelin system in alcohol-related behaviors illuminating the possibility of using ghrelin receptor blockers as a pharmacological intervention for alcohol use disorder (AUD). Preliminary data from a recently conducted phase 1b human study with a ghrelin receptor inverse agonist, PF-5190...
Article
Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the in vivo biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additionally, radioligands that can image changes in endogenous adenosine levels in different physiolo...
Article
Background and purpose: Maintenance treatment with opioid agonists (buprenorphine, methadone) decreases opioid use and relapse. We recently modeled maintenance treatment in rats and found that chronic delivery of buprenorphine or the mu opioid receptor (MOR) partial agonist TRV130 decreases relapse to oxycodone seeking and taking. Here, we tested...
Article
Impulsive action can be defined as the inability to withhold a response and represents one of the dimensions of the broad construct impulsivity. Here, we characterized a modified differential reinforcement of low rates of responding (DRL) task developed in our laboratory, in which impulsive action is measured in ad libitum fed/watered subjects. Spe...
Article
A subset of rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) develop unusually high levels of drug-taking. A history of responding maintained by cocaine, but not food, prevents the development of this high-responder phenotype; however, it is unclear how histories of non-contingent cocaine exposure or self-administering drugs from oth...
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Opioid use disorders and fatal overdose due to consumption of fentanyl-laced heroin remain a major public health menace in the United States. Vaccination may serve as a promising potential remedy to combat accidental overdose and to mitigate the abuse potential of opioids. We previously reported the heroin and fentanyl monovalent vaccines carrying,...
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Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to ne...
Article
Background Alcohol Use Disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as by hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma-1 Receptors (Sig-1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig-1R hypera...
Article
The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting the dopamine D3 receptor (D3R) with highly selective antagonists/partial agonists can reduce opioid self-admin...
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[This corrects the article DOI: 10.3389/fnbeh.2020.00153.].
Article
Active immunization is being explored as a potential therapeutic to combat accidental overdose and to mitigate the abuse potential of opioids. Hapten design is one of the crucial factors that determines the efficacy of a candidate vaccine to substance abuse and remains one of the most active areas of research in vaccine development. Herein we repor...
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RationaleOxycodone is one of the most commonly prescribed and most frequently abused opioid analgesics, yet little is known regarding individual vulnerabilities to oxycodone abuse. The synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) has been shown to produce a “high-responder” phenotype characterized by increased drug intake and respondin...
Article
Methylone's rewarding effects have been well characterized; however, little is known about its aversive effects and how such effects may be impacted by sex. In this context, the present study investigated the aversive effects of methylone (vehicle, 5.6, 10 or 18 mg/kg, IP) in 35 male and 31 female Sprague-Dawley rats assessed by conditioned taste a...
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Although opioids are potent analgesics, a consequence of chronic opioid use is hyperalgesia during withdrawal, which may contribute to opioid misuse. Dynorphin, the endogenous ligand of κ-opioid receptors (KORs), is upregulated in opioid-dependent rats and in animal models of chronic pain. However, the role of KORs in opioid withdrawal-induced hype...
Article
3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance with stimulant properties and potential for abuse. Despite its popularity, limited studies have examined relationships between brain concentrations of methylone, its metabolites, and pharmacodynamic effects. The goal of the present study was two-fold: 1) to determine p...
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Full-text available
Rationale A subset of male rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) have unusually high levels of drug intake; however, factor(s) that influence this behavior (e.g., reinforcement history and sex) are unknown. Objectives Characterize the reinforcing potency and effectiveness of MDPV in female rats to determine whether (1) a...
Article
The 3,4-methylenedioxypyrovalerone (MDPV), and other structurally related synthetic cathinones, are popular alternatives to prototypical illicit psychostimulants, such as cocaine and methamphetamine. These drugs are often referred to as 'bath salts' and function either as cocaine-like inhibitors of monoamine uptake, or amphetamine-like substrates f...
Article
Neuropathic pain is a major symptom of multiple sclerosis (MS) with up to 92% of patients reporting bodily pain, and 85% reporting pain severe enough to cause functional disability. None of the available therapeutics target MS pain. Toll-like receptors 2 and 4 (TLR2/TLR4) have emerged as targets for treating a wide array of autoimmune disorders, in...
Article
Post-operative cognitive dysfunction (POCD) is the collection of impaired cognitive symptoms, lasting days to months, experienced by individuals following a surgery. Persistent POCD is most commonly experienced by older individuals and is associated with a greater vulnerability to developing Alzheimer’s disease, but the underlying mechanisms are no...
Article
More than a quarter of veterans of the 1990-1991 Persian Gulf War suffer from Gulf War Illness (GWI), a chronic, multi-symptom illness that commonly includes musculoskeletal pain. Exposure to a range of toxic chemicals, including sarin nerve agent, are a suspected root cause of GWI. Moreover, such chemical exposures induce a neuroinflammatory respo...
Article
Dietary supplements often contain additives not listed on the label, including a-ethyl homologs of amphetamine such as N,a-diethylphenethylamine (DEPEA). Here we examined the neurochemical and cardiovascular effects of a-ethylphenethylamine (AEPEA), N-methyl-a-ethylphenethylamine (MEPEA), and DEPEA as compared to the effects of amphetamine. All dru...
Article
Multiple sclerosis (MS) is associated with burdensome memory impairments. Preclinical literature suggests that these impairments are linked to neuroinflammation. Previously, we have shown that toll-like receptor 4 (TLR4) antagonists, such as (+)-naltrexone [(+)-NTX], block neuropathic pain and associated spinal inflammation in rats. Here we extend...
Article
A deuterated hapten was designed and synthesized that will be essential for a future study of residual hapten and stability of a hapten-protein conjugate. This hapten, 6-AmHap, was chosen for a heroin vaccine that is now slated for a Phase 1 clinical trial. A maleimide-thiol bioconjugation strategy was successfully applied to our heroin vaccine to...
Article
Depression is a leading cause of disability worldwide and current treatments are often inadequate for many patients. Increasing evidence indicates that inflammation contributes to susceptibility to depression. We hypothesized that targeting Toll-like receptor 4 (TLR4), one of the main signaling pathways for triggering an inflammatory response, woul...
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The time-dependent increase in cue-triggered opioid seeking, termed “incubation of opioid craving,” is modeled in rodents by examining responding for opioid-associated cues after a period of forced abstinence. With opioid drugs, withdrawal symptoms may heighten cue reactivity by recruiting brain systems involved in both reward seeking and stress re...
Article
Active immunization is an emerging potential modality to combat fatal overdose amid the opioid epidemic. In this study, we described the design, synthesis, formulation, and animal testing of an efficacious vaccine against fentanyl. The vaccine formulation is composed of a novel fentanyl hapten conjugated to tetanus toxoid (TT) and adjuvanted with l...
Article
A series of compounds have been synthesized with a variety of substituents based on a three-carbon chain at the C9-position of 3-hydroxy-N-phenethyl-5-phenylmorphan (3-(2-phenethyl-2-azabicyclo[3.3.1]nonan-5-yl)phenol). Three of these were found to be μ-opioid receptor agonists in the inhibition of forskalin-induced cAMP accumulation assay and they...
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(−)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPγS binding, forskolin-induced cAMP accumulation assay, and MOR-mediated β-arrestin recruitment assays). “Body” and “tail” interactions with opioid receptors (a subs...
Article
The present series of studies examine the impact of systemically administered therapeutics on peripheral nerve injury (males; unilateral sciatic chronic constriction injury [CCI])‐induced suppression of voluntary wheel running, across weeks after dosing cessation. Following CCI, active phase running distance and speed are suppressed throughout the...
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Delta opioid receptor (δ-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animal models. However, the role of agonist efficacy in generating different δ-receptor-mediated behaviors has not been thoroughly investigated. To this end, efficacy requirements for δ-receptor-mediated antihyperalgesia, antidepres...
Article
Many drugs of abuse are mixed with other psychoactive substances (e.g., caffeine) prior to their sale or use. Synthetic cathinones (e.g., 3,4-methylenedioxypyrovalerone [MDPV]) are commonly mixed with caffeine or other cathinones (e.g., 3,4-methylenedioxy-N-methylcathinone [methylone]), and these "bath salts" mixtures (e.g., MDPV + caffeine) can ex...
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Every year, 15 million pregnancies end prematurely, resulting in more than 1 million infant deaths and long‐term health consequences for many children. The physiological processes of labour and birth involve essential roles for immune cells and pro‐inflammatory cytokines in gestational tissues. There is compelling evidence that the mechanisms under...
Conference Paper
Despite decades of research, the behavioral, pharmacological, and neurobiological determinants of one’s vulnerability to develop a substance use disorder are not well understood. When rats are allowed to self-administer cocaine under short-access conditions, patterns of drug intake tend to be well-regulated; however, manipulating drug access condit...
Article
Pain is more prevalent in women for reasons that remain unclear. We have identified a mechanism of injury-free nociceptor sensitization and opioid-induced hyperalgesia (OIH) promoted by prolactin (PRL) in females. PRL signals through mutually inhibitory long (PRLR-L) and short (PRLR-S) receptor isoforms, and PRLR-S activation induces neuronal excit...
Article
Spontaneous preterm labor is frequently caused by an inflammatory response in the gestational tissues elicited by either infectious or sterile agents. In sterile preterm labor, the key regulators of inflammation are not identified, but platelet activating factor (PAF) is implicated as a potential rate-limiting effector agent. Since toll-like recept...
Article
A previous study from our laboratory has shown that the selective catecholamine reuptake inhibitor 3,4-methylenedioxypyrovalerone (MDPV) persistently alters impulsive choice as measured by delay discounting. To further understand the proimpulsive effects of MDPV, we examined its capacity to modulate a different impulsive measure - impulsive action...
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Rationale Approximately 20 million adults in the USA have an alcohol use disorder (AUD). There are clinical and preclinical data suggesting that psychedelics may have benefits for AUD. Objective To investigate the effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on the behavioral effects of ethanol. Methods The effects o...
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Rationale The availability and abuse of synthetic analogues of cathinone have increased dramatically around the world. Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone [MDPV] and α-pyrrolidinopentiophenone [α-PVP], are cocaine-like inhibitors of monoamine transporters and common constituents of “bath salts” or “flakka” preparations. Stu...
Article
The opioid epidemic has become a severe public health problem, with approximately 130 opioid‐induced deaths occurring each day in the United States. Prescription opioids are responsible for approximately 40% of these deaths. Oxycodone is one of the most commonly abused prescription opioids, but despite its prevalent misuse, the number of preclinica...
Article
The synthetic cathinone α-pyrrolidinovalerophenone (α-PVP) continues to be abused despite being banned by regulatory agencies. The abused formulation of α-PVP is a racemic mixture consisting of two enantiomers, S-α-PVP and R-α-PVP. In this study, we investigated the neurochemical, behavioral, and cardiovascular effects of racemic α-PVP and its enan...
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Identifying neurons that have functional opioid receptors is fundamental for the understanding of the cellular, synaptic and systems actions of opioids. Current techniques are limited to post hoc analyses of fixed tissues. Here we developed a fluorescent probe, naltrexamine-acylimidazole (NAI), to label opioid receptors based on a chemical approach...
Article
Inflammation elicited by infection or non-infectious insults during gestation induces pro-inflammatory cytokines that can shift the trajectory of development to alter offspring phenotype, promote adiposity and increase susceptibility to metabolic disease in later life. Here we utilize mice to investigate the utility of a small molecule TLR4 antagon...
Article
Rationale The majority of synthetic cathinone research has used only male subjects, and as a result there are few studies assessing the impact of biological sex on their effects. Objectives The current work extends the characterization of the second-generation synthetic cathinone, α-PVP, by investigating how biological sex impacts α-PVP's aversive...