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Articles 1 - 10 of 10
Full-Text Articles in Life Sciences
Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls
Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls
Jarrod Bailey, PhD
Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …
An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls
Jarrod Bailey, PhD
Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …
Insular Cortex Lesions And Morphine-Induced Suppression Of Conditioned Stimulus Intake In The Rat, Christopher T. Roman, Steve Reilly
Insular Cortex Lesions And Morphine-Induced Suppression Of Conditioned Stimulus Intake In The Rat, Christopher T. Roman, Steve Reilly
Christopher Roman
The present experiment examined the influence of insular cortex (IC) lesions on the intake of a taste stimulus in a consummatory procedure that used morphine as the unconditioned stimulus. In normal rats, morphine caused a rapid reduction in saccharin intake when the taste was novel but not when it was familiar. Irrespective of stimulus novelty, morphine had little influence on the saccharin consumption of IC-lesioned rats. The results are discussed in terms of a lesion-induced disruption of (i) a reward comparison mechanism and (ii) the perception of taste novelty.
Taste, Olfactory And Trigeminal Neophobia In Rats With Forebrain Lesions, Jian-You Lin, Christopher T. Roman, Justin St. Andre, Steve Reilly
Taste, Olfactory And Trigeminal Neophobia In Rats With Forebrain Lesions, Jian-You Lin, Christopher T. Roman, Justin St. Andre, Steve Reilly
Christopher Roman
The present study was designed to examine whether lesions of the insular cortex (IC; Experiment 1), the basolateral amygdala (BLA) or medial amygdala (MeA; Experiment 2) influence the neophobic reactions to orally consumed liquid stimuli. Three different types of stimuli were used: taste (0.5% saccharin), olfactory (0.1% amyl acetate), and trigeminal (0.01 mM capsaicin). Rats with IC, BLA and MeA lesions showed normal responses to the olfactory and trigeminal stimuli. Each type of lesion, however, disrupted the initial occurrence of neophobia to the taste stimulus. The significance of these findings to conditioned taste aversion is discussed.
Taste-Potentiated Odor Aversion Learning In Rats With Lesions Of The Insular Cortex, Jian-You Lin, Christopher T. Roman, Steve Reilly
Taste-Potentiated Odor Aversion Learning In Rats With Lesions Of The Insular Cortex, Jian-You Lin, Christopher T. Roman, Steve Reilly
Christopher Roman
The current study assessed the influence of excitotoxic lesions of the insular cortex (IC) on tastepotentiated odor aversion (TPOA) learning. Water-deprived rats initially received a single odortoxicosis or odor/taste-toxicosis pairing and were subsequently tested, in separate trials, with the odor and the taste stimulus. Indicating TPOA, neurologically intact rats conditioned with the odor/taste compound stimulus acquired significantly stronger odor aversions than normal rats conditioned with the odor stimulus. IC lesions disrupted TPOA, conditioned taste aversion and taste neophobia. The finding that taste did not potentiate odor aversion learning in the IC lesioned rats provides support for the “within-compound association” analysis …
Taste Neophobia And C-Fos Expression In The Rat Brain, Jian-You Lin, Christopher T. Roman, Joe Arthurs, Steve Reilly
Taste Neophobia And C-Fos Expression In The Rat Brain, Jian-You Lin, Christopher T. Roman, Joe Arthurs, Steve Reilly
Christopher Roman
Taste neophobia refers to a reduction in consumption of a novel taste relative to when it is familiar. To gain more understanding of the neural basis of this phenomenon, the current study examined whether a novel taste (0.5% saccharin) supports a different pattern of c-Fos expression than the same taste when it is familiar. Results revealed that the taste of the novel saccharin solution evoked more Fos immunoreactivity than the familiar taste of saccharin in the basolateral region of the amygdala, central nucleus of the amygdala, gustatory portion of the thalamus, and the gustatory insular cortex. No such differential expression …
Effects Of Insular Cortex Lesions On Conditioned Taste Aversion And Latent Inhibition In The Rat, Christopher T. Roman, Steve Reilly
Effects Of Insular Cortex Lesions On Conditioned Taste Aversion And Latent Inhibition In The Rat, Christopher T. Roman, Steve Reilly
Christopher Roman
The present study tested the hypothesis that lesions of the insular cortex of the rat retard the acquisition of conditioned taste aversions (CTAs) because of an impairment in the detection of the novelty of taste stimuli. Demonstrating the expected latent inhibition effect, nonlesioned control subjects acquired CTAs more rapidly when the conditioned stimulus (0.15% sodium saccharin) was novel rather than familiar (achieved by pre-exposure to the to-be-conditioned taste cue). However, rats with insular cortex lesions acquired taste aversions at the same slow rate regardless of whether the saccharin was novel or familiar. The pattern of behavioural deficits obtained cannot be …
Morphine-Induced Suppression Of Conditioned Stimulus Intake: Effects Of Stimulus Type And Insular Cortex Lesions, Jian-You Lin, Christopher T. Roman, Steve Reilly
Morphine-Induced Suppression Of Conditioned Stimulus Intake: Effects Of Stimulus Type And Insular Cortex Lesions, Jian-You Lin, Christopher T. Roman, Steve Reilly
Christopher Roman
Intake of an unconditionally preferred taste stimulus (e.g., saccharin) is reduced by contingent administration of a drug of abuse (e.g., morphine). We examined the influence of insular cortex (IC) lesions on morphine-induced suppression of an olfactory cue and two taste stimuli with different levels of perceived innate reward value. Two major findings emerged from this study. First, morphine suppressed intake of an aqueous odor as well as each taste stimulus in neurologically intact rats. Second, IC lesions disrupted morphine-induced suppression of the taste stimuli but not the aqueous odor cue. These results indicate that the perceived innate reward value of …
Basolateral Amygdala And Morphine-Induced Taste Avoidance In The Rat, Jamie Lovaglio, Jian-You Lin, Christopher T. Roman, Steve Reilly
Basolateral Amygdala And Morphine-Induced Taste Avoidance In The Rat, Jamie Lovaglio, Jian-You Lin, Christopher T. Roman, Steve Reilly
Christopher Roman
The present experiment examined the influence of excitotoxic lesions of the basolateral amygdala (BLA) on morphine-induced saccharin avoidance. Neurologically intact subjects rapidly learned to avoid drinking the taste conditioned stimulus (CS), an effect that was sustained throughout the experiment. Although the BLA-lesioned (BLAX) rats showed CS avoidance over the first few trials, the effect was not sustained. That is, by the end of the experiment, the BLAX rats were drinking the same amount of saccharin after seven saccharin-morphine trials as they did on the first trial (i.e., prior to the morphine injections). Potential interpretations of the results are discussed including …
Conditioned Taste Aversion And Latent Inhibition Following Extensive Taste Preexposure In Rats With Insular Cortex Lesions, Christopher T. Roman, Jian-You Lin, Steve Reilly
Conditioned Taste Aversion And Latent Inhibition Following Extensive Taste Preexposure In Rats With Insular Cortex Lesions, Christopher T. Roman, Jian-You Lin, Steve Reilly
Christopher Roman
Lesions of the insular cortex (IC) attenuate acquisition of conditioned taste aversions (CTAs). We have suggested that this impairment is the expected consequence of a failure of IC-lesioned (ICX) rats to recognize unfamiliar taste stimuli as novel. That is, ICX rats treat novel taste stimuli as if they are familiar and as a result show a latent inhibition-like retardation of learning. This account anticipates that ICX rats should acquire CTAs at the same slow rate as normal rats that are familiar with the taste stimulus. The present experiment confirmed this hypothesis in a design that compared CTA acquisition in normal …