Biology subjects

Neill, J.

Publications and source records attributed to Neill, J..

3 recordsLinked to original sources

bioRxiv2023

Rate dependent effects of SKF 38393 and amphetamine on waiting impulsivity in the 5C-CPT

RationaleStimulants are the first-line treatment for attention-deficit/hyperactivity disorder (ADHD). However, the ensuing risk of abuse with stimulants means there is an urgent need for new, low-risk therapeutic agents. D1 receptors play an important role in the cognitive enhancing effects of stimulants and thus may provide a therapeutic target. Previous pre-clinical studies have shown that selective activation of D1 receptors improves sustained attention in the 5C-CPT without improving waiting impulsivity (premature response). ObjectiveThe aim of the present experiment was to compare the effects of the selective D1 receptor agonist SKF 38393 to a standard ADHD treatment (amphetamine) on waiting impulsivity in the 5C-CPT under extended inter-trial intervals. Oldhams method was used to determine the presence of a rate-dependent effect. MethodsAdult female Lister hooded rats were trained to criterion in the 5C-CPT (>70% accuracy, < 30% omission and < 40% false alarms). Effects of the selective D1 receptor agonist SKF 38393 (2-6 mg/kg) or amphetamine (0.1-0.4 mg/kg) were investigated under behavioural manipulations to challenge inhibitory response control. ResultsThe highest dose of SKF 38393 and the two highest doses of amphetamine improved waiting impulsivity in a baseline dependent manner. The clockwise movement of the regression line indicates that, as the dose increases, the magnitude of improvement increases in a manner consistent with baseline performance. ConclusionsThese findings support further clinical investigation of D1 receptor modulators to facilitate the discovery of improved medications for impulsive behaviour related disorders such as ADHD. The concept of rate dependency applies to effects of SKF 38393 or amphetamine on waiting impulsivity. Oldhams correlation method may present an opportunity to enhance the translational value of research in the preclinical laboratory to the clinic.

animal behavior and cognition↗

bioRxiv2023

The dopamine inhibitor GBR12909 improves attention and compulsive behaviour in female rats

BackgroundStimulants such as methylphenidate are the first-line treatment for attention deficit hyperactivity disorder (ADHD). A principal mechanism of action for these drugs is to reduce dopamine reuptake in the striatum. However, the ensuing risk of abuse with such stimulants means there is an urgent need for new, low-risk therapeutic agents. GBR12909 is a highly selective dopamine reuptake inhibitor, making it an important experimental tool. Indeed, this drug completed Phase II clinical trials for treatment of cocaine abuse. Understanding such drugs has the potential to expand our understanding of the striatal dopamine contribution to impulsivity, attention and compulsive behaviour and will help the development of novel targeted treatments for ADHD without an abuse risk. AimsThe aim of this work was to examine the role of low doses of GBR12909 on attention, impulsivity and compulsive behaviour as measured by 5C-CPT. Oldhams methods was used to determine the presence of a rate-dependent effect. MethodsFemale Lister hooded rats were trained to criterion in the 5C-CPT (>70% accuracy, < 30% omission and < 40% false alarms). Effects of GBR12909 (0.25-1 mg/kg) were investigated on attention, impulsivity and compulsive behaviour under challenging task conditions. ResultsThe two lowest doses of GBR12909 improved selective attention in a rate-dependent manner while the highest dose of GBR 12909 showed a tendency toward improving compulsive behaviour in a baseline-dependent manner. However, GBR 12909 impaired waiting impulsivity in a baseline-dependent manner. ConclusionsGBR12909 has a clearly beneficial effect on attention and compulsive behaviour in the female rat. These findings support further clinical investigation of GBR-type dopamine uptake blockers or GBR analogues to facilitate the discovery of medications for inattentive ADHD, stimulant abuse, compulsive drug seeking behaviour and obsessive-compulsive disorder.

animal behavior and cognition↗

bioRxiv2021

Twenty-one Year Trends for Shorebirds, Waterfowl, and Other Waterbirds at Great Salt Lake, Utah

Millions of wetland-dependent birds annually depend on saline lakes and associated wetlands in the western United States. Understanding the population status and trends of birds with different life histories and habitats can guide efforts to secure water resources needed to sustain bird habitats. We used a 21-year dataset to examine population trends for 24 survey units presumed to be high-quality habitat for migratory shorebirds, waterfowl, and other waterbirds at Great Salt Lake and associated wetlands. As expected for high-quality habitats, we found stable or positive trends for 36 of 37 species or groups in fall, spring, or both seasons when considering survey units in aggregate. Despite stable or positive aggregate trends, negative trends did occur in some individual survey units. Foraging, migration distance, and taxonomic groupings were unrelated to trend direction. Research is needed to test whether survey units represent high-quality habitat. With declining regional water resources, stable and positive aggregate trends reinforce the importance of surveyed units at Great Salt Lake and associated wetlands to wetland-dependent birds. Ensuring continuation of stable and positive trends will require identifying environmental factors - including water quantity and quality - driving trends, and require coordinated regional management and monitoring of wetland-dependent birds.

ecology↗