Publications by authors named "Kimberly G Freeman"

Article Synopsis
  • The study aims to explore how the composition of gut microbiota influences reward signaling and the role of the vagus nerve in communication between microbiota and the brain.
  • Male germ-free Fisher rats were colonized with gut contents from either low-fat or high-fat fed rats to observe behavioral changes related to food consumption.
  • Results show that high-fat (ConvHF) rats ate more but motivated less for high-fat foods and had lower dopamine levels and receptor expression in the brain's reward center, indicating that gut bacteria can significantly affect feeding behavior through the vagus nerve.
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Previous work has shown that cannabinoids increase feeding, while cholecystokinin (CCK) has an anorexigenic effect on food intake. Receptors for these hormones are located on cell bodies of vagal afferent nerves in the nodose ganglia. An interaction between CCK and endocannabinoid receptors has been suggested.

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Multiple sclerosis (MS) is an autoimmune disease that affects the CNS, resulting in accumulated loss of cognitive, sensory, and motor function. This study evaluates the neuropathological effects of voluntary exercise in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Two groups of C57BL/6J mice were injected with an emulsion containing myelin oligodendrocyte glycoprotein and then randomized to housing with a running wheel or a locked wheel.

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  • Relapse is a major challenge in long-term drug addiction treatment, particularly with cocaine, which increases dopamine levels and drives craving behavior.
  • Research shows that the neuropeptide galanin and its synthetic analog, galnon, can reduce the rewarding effects of cocaine and mitigate hyperactivity and relapse behaviors in rats without affecting overall motor functions or food-seeking behaviors.
  • These findings suggest that targeting the dopamine system with compounds like galnon could be a promising strategy for treating cocaine dependence.
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Objective: To determine and compare the ratio of uracil (U) to dihydrouracil (UH(2)) concentrations in plasma as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency.

Animals: 101 client- and shelter-owned dogs.

Procedures: Study dogs included 74 clinically normal dogs, 17 dogs with neoplasia, and 10 dogs with renal insufficiency.

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Lesch-Nyhan disease (LND) is a severe X-linked neurological disorder caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT). In contrast, HPRT-deficiency in the mouse does not result in the profound phenotypes such as self-injurious behavior observed in humans, and the genetic basis for this phenotypic disparity between HPRT-deficient humans and mice is unknown. To test the hypothesis that HPRT deficiency is modified by the presence/absence of phosphoribosyltransferase domain containing 1 (PRTFDC1), a paralog of HPRT that is a functional gene in humans but an inactivated pseudogene in mice, we created transgenic mice that express human PRTFDC1 in wild-type and HPRT-deficient backgrounds.

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Article Synopsis
  • Disulfiram (Antabuse) inhibits an enzyme called aldehyde dehydrogenase (ALDH), leading to unpleasant reactions when alcohol is consumed, which helps deter drinking.
  • Disulfiram may also reduce cocaine use through mechanisms unrelated to ALDH, possibly by inhibiting dopamine β-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine.
  • In rat studies, disulfiram reduced norepinephrine levels and effectively blocked relapse to cocaine-seeking behavior when triggered by the drug, while a similar selective DBH inhibitor showed comparable effects without impacting food-seeking behavior.
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Previous studies of hepatic insulin gene therapy (HIGT) focused on glycemic effects of insulin produced from hepatocytes. In this study, we extend the observations of glycemic control with metabolically regulated HIGT to include systemic responses and whole-body metabolism. An insulin transgene was administered with an adenoviral vector [Ad/(GlRE)(3)BP1-2xfur] to livers of BB/Wor rats made diabetic with polyinosinic polycytidilic acid (poly-I:C) (HIGT group), and results compared with nondiabetic controls (non-DM), and diabetic rats receiving different doses of continuous-release insulin implants (DM-low BG and DM-high BG).

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Olfactory bulbectomy (OBX) in rats produces behavioral, physiological, and neurochemical changes that resemble symptoms of depression in humans. The procedure thus serves as a rodent model of affective disorder. Many of the behavioral effects of OBX resemble psychomotor agitation.

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Cannabinoids have been shown to influence food intake, and until recently, the neural pathways mediating these effects have remained obscure. It has been previously shown that intracerebroventricular injection of delta-9-tetrahydrocannabinol (Delta(9)-THC) causes increased consumption of palatable foods in rats, and we postulated the involvement of the hindbrain in this cannabinoid-induced food intake. Cannulated rats (both female and male groups) trained to consume sweetened condensed milk received either lateral or fourth ventricle injections of CP 55,940 and were presented with sweetened condensed milk 15 min after injection.

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