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Transplacental Cocaine Exposure: Behavioral Consequences
Published in Richard J. Konkol, George D. Olsen, Prenatal Cocaine Exposure, 2020
Aaron S. Wilkins, Barry E. Kosofsky, Anthony G. Romano, John A. Harvey
There are several different forms of attention, including selective attention, divided attention, and sustained attention, which includes vigilance.39 Deficits in mechanisms underlying these forms of attention may result in specific impairments in performance in humans and rodents. In normal humans, treatment with IV clonidine, a noradrenergic alpha2 agonist, impairs attentional performance.40–43 In rats, Robbins and colleagues found that performance in tasks requiring attention can be disrupted by lesioning the dorsal noradrenergic bundle (DNAB).44,45 In a visual discrimination task (5-choice serial reaction time task), rats were required to detect brief visual stimuli presented unpredictably at one of five locations and then push a panel paired with the stimulus. Animals with the DNAB lesions displayed deficits in attention in this task when a) loud bursts of white noise were interpolated immediately prior to each visual stimulus,44 b) the stimuli were presented unpredictably in time,46 and c) the rats were treated with amphetamine, which caused impulsive and premature responding.47 Thus the noradrenergic system is believed to be involved in attentional processing.39,46,48,49 Yet researchers have found that lesions of the dopaminergic,48 serotonergic,50 or cholinergic51 systems also disrupt attention. According to Robbins and Everitt,49 these systems probably interact in modulating attention.
Neuropsychology of Cognitive Aging in Rodents
Published in David R. Riddle, Brain Aging, 2007
Joshua S. Rodefer, Mark G. Baxter
The effects of aging on performance in attention-related tasks have been somewhat limited by the number of rodent models that assess frontal cognition. Muir et al. [96] demonstrated age-related changes in attentional functioning in 7- vs. 13- to 14-month-old rats in the 5-choice serial reaction time task by manipulating the attentional loading of the task. Subsequently, as animals aged, the difference between younger (10 to 11 months old) and aged (23 to 24 months old) performance became greater, such that significant differences in performance could be observed in baseline measures without any manipulations of the attentional load of the task. This was similar to results reported by Grottick and Higgins [97], who found that aged (24 months old) rats were impaired in 5-CSRTT performance compared to younger (12 months old) subjects. Increasing the difficulty of the task impaired the performance of younger rats, producing comparable performance to older rats. Likewise, decreasing the task difficulty for older subjects produced performance comparable to younger animals.
High fat diet consumption restricted to adolescence has minimal effects on adult executive function that vary by sex
Published in Nutritional Neuroscience, 2022
Animals next moved on to 5 Choice Serial Reaction Time Task (5CSRTT training). Following a 30 s intertrial interval, one of the five stimulus areas would light up. The mouse had to touch the lit stimulus in order to receive reinforcer and record a correct trial. A premature trial was recorded if the animal made a response during the ITI. If an animal responded to an unlit stimulus, then an incorrect trial was recorded. If no response was made, then an omitted trial was recorded. Animals moved through 3 progressively more difficult 5CSRTT schedules, as defined by decreasing stimulus length (Session 10: 16 s, Session 11: 8 s, Session 12: 4 s). Criterion to move to the next difficulty was >20 responses with 50% correct for 2 consecutive days. The second day at criterion performance was analyzed.
Bundling arrows: improving translational CNS drug development by integrated PK/PD-metabolomics
Published in Expert Opinion on Drug Discovery, 2018
W. J. van den Brink, T. Hankemeier, P. H. van der Graaf, E. C. M. de Lange
Current translational CNS drug development highly relies on behavioral endpoints, such as the 5-choice serial reaction time task. While these end points may provide reasonable construct validity, their predictive validity is low [15,16]. Predictive validity, which includes a mechanistic rationale between the drug effect and the end point, is important to translate the preclinical to the clinical pharmacology [17]. It is therefore that biomarkers are increasingly recognized as an essential element of CNS drug development [7,18–20]. Indeed, biomarkers have been defined as indicators of specific pharmacological or physiological processes [21,22]. Current biomarker strategies include receptor occupancy [23–25], functional imaging [26,27], biochemical measures in CSF [20], EEG [28,29], or physiological measures such as hormone release [30]. Biomarkers have been classified into multiple pharmacological levels following the causal relation of the drug dose to the clinical effect [31]. These are (i) genotype or phenotype, (ii) drug exposure, (iii) target occupancy, (iv) target activation, (v) physiological/laboratory measures, (vi) disease processes, (vii) clinical scales. Such classification provides a framework for rational drug development. In particular, as depicted in Figure 1, confidence in the drug exposure, target binding, and target activation are key components to guarantee successful translational drug development [12].