Neuromodulating mice and men: Are there functional species differences in neurotransmitter concentration?

Fitzgerald, Paul J.

doi:10.1016/j.neubiorev.2009.04.003

Cited by 20 publications

(21 citation statements)

References 66 publications

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“…Significant biological differences between rodents and humans could lead to erroneous predictions of the activity of potential therapeutics (Fitzgerald 2009; Huggins et al. 2012; Chen et al.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin‐induced neuropathic cold hypersensitivity

Shidahara

Ogawa

Nakamura

et al. 2016

Pharmacology Res & Perspec

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Oxaliplatin is a first‐line treatment for colorectal cancer. However, shortly following treatment, cold‐evoked hypersensitivity appears in the extremities and over time, the pain is such that oxaliplatin dosing may need to be markedly reduced or even terminated. There is currently a lack of efficacious treatments for oxaliplatin‐induced peripheral neuropathy, which is due in part to the difficulty in translating findings obtained from preclinical rodent models of chemotherapy‐induced peripheral neuropathy. Nonhuman primates (NHP) are phylogenetically closer to humans than rodents and may show drug responses that parallel those of humans. A significant decrease in tail withdrawal latency to 10°C water (“cold hypersensitivity”) was observed beginning 3 days after intravenous infusion of oxaliplatin (5 mg/kg) in Macaca fascicularis. A single treatment of duloxetine (30 mg/kg, p.o.) ameliorated oxaliplatin‐induced cold hypersensitivity, whereas pregabalin (30 mg/kg, p.o.) and tramadol (30 mg/kg, p.o.) did not. By contrast, in rats, no significant cold hypersensitivity, or increased responsiveness to acetone applied to the hind paws, was observed 3 days after the first injection of oxaliplatin (5 mg/kg, i.p., once per day, two injections). Therefore, rats were tested after six treatments of oxaliplatin, 17 days after the first treatment. All analgesics (30 mg/kg, p.o.) significantly ameliorated cold hypersensitivity in rats. The activity of analgesics in the oxaliplatin‐treated macaques parallel clinical findings. The current results indicate that the NHP could serve as a bridge species to improve translatability of preclinical findings into clinically useful treatments for oxaliplatin‐induced peripheral neuropathy.

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Section: Introductionmentioning

confidence: 99%

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin‐induced neuropathic cold hypersensitivity

Shidahara

Ogawa

Nakamura

et al. 2016

Pharmacology Res & Perspec

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“…Another limitation is the validity of comparing rodent models of anxiety-and depression-related behavior with human drug treatment of major depression, but at least the same drugs are being used in rodents and humans in many of these studies. A fairly recent study suggested that putative differences in modulatory neurotransmitter concentration between rodents and primates (possibly including humans) could affect species differences in speed of drug response [2]. These putative species differences in transmitter systems may negatively impact our ability to compare speed of drug response between rodents and humans, possibly by affecting the proportionality argument put forth here.…”

Section: Discussionmentioning

confidence: 80%

“…While this paper very briefly examines some studies in which antidepressants have been administered to persons for a year or longer, the main point here addresses a proposed relationship between speed of drug response in rodents versus humans, to estimate time to reach maximum effect in humans [2]. In doing so, this paper puts forth the hypothesis that monoaminergic antidepressants take multiple years to reach maximum effect in humans.…”

Section: Introductionmentioning

confidence: 99%

Forbearance for fluoxetine: Do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?

Fitzgerald

2013

International Journal of Neuroscience

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It is of high clinical interest to better understand the timecourse through which psychiatric drugs produce their beneficial effects. While a rough estimate of the time lag between initiating monoaminergic antidepressant therapy and the onset of therapeutic effect in depressed subjects is two weeks, much less is known about when these drugs reach maximum effect. This paper briefly examines studies that directly address this question through long-term antidepressant administration to humans, while also putting forth a simple theoretical approach for estimating the time required for monoaminergic antidepressants to reach maximum therapeutic effect in humans. The theory invokes a comparison between speed of antidepressant drug response in humans and in rodents, focusing on the apparently greater speed in rodents. The principal argument is one of proportions, comparing earliest effects of these drugs in rodents and humans, versus their time to reach maximum effect in these organisms. If the proportionality hypothesis is even coarsely accurate, then applying these values or to some degree their ranges to the hypothesis, may suggest that monoaminergic antidepressants require a number of years to reach maximum effect in humans, at least in some individuals.

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“…It is well-known that mental status, which is accompanied by changes in levels of various hormones (Kolber et al, 2008), neuromodulators (Fitzgerald, 2009), and the activation of specific brain regions (Kolber et al, 2009), is an important factor that affects the overt behavior of an animal. Considering this, it is likely that mental status can also affect the determination of P BE .…”

Section: Discussionmentioning

confidence: 99%

Determination of Behavior and the Stimuli-dependent Transition of the Probability of Behavioral Expression: A Study on the Fluctuation of Behavioral State as Represented by the Level of Body Movement Suppression

Lee

Kaang

2009

Exp Neurobiol

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The behavior of most animals is extremely complex. Despite accumulating knowledge about the mechanisms of neurons and nervous systems, which regulate these complex behaviors, we have little understanding about how these mechanisms function. In the present study, we analyzed the exploratory behavior of mice repeatedly exposed to a novel context and tracked the changes in the fluctuation patterns of the accumulated level of body movement suppression (BMS). As a result, we found that the fluctuation in BMS can be divided into two phases, which show a pattern of progressive transition from the initial state to the context-dependent and stable equilibrium state. In the former, transition phase, the level of BMS was easily affected by the number of exposures and mental status of mice. However, in the latter, equilibrium phase, the level of BMS was only dependent on the environmental stimuli involved in the context. On the basis of the results, we suggests here a model that explains the determination of complex behavior observed in higher animals by means of the probability of behavioral expression.

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Neuromodulating mice and men: Are there functional species differences in neurotransmitter concentration?

Cited by 20 publications

References 66 publications

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin‐induced neuropathic cold hypersensitivity

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin‐induced neuropathic cold hypersensitivity

Forbearance for fluoxetine: Do monoaminergic antidepressants require a number of years to reach maximum therapeutic effect in humans?

Determination of Behavior and the Stimuli-dependent Transition of the Probability of Behavioral Expression: A Study on the Fluctuation of Behavioral State as Represented by the Level of Body Movement Suppression

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