Genetic influences on drug‐induced psychomotor activation in mice
Bibliographic record
Abstract
A number of processes are important in the development of substance dependence including initial sensitivity to the acute pharmacological effects of drugs/alcohol. The objectives of the present study were (1) to identify quantitative trait loci (QTLs) associated with the initial sensitivity to the effects of morphine in the A/J, C57BL/6J and AXB/BXA recombinant inbred strains of mice; (2) to identify potential commonalities in the chromosomal regions associated with morphine, cocaine and ethanol sensitivity using multiple-trait genetic analysis and (3) to determine whether there were interstrain differences in dopamine uptake and transporter binding. Initial sensitivity to morphine was determined by measuring locomotor activity in a computerized open-field apparatus following acute morphine administration (0, 10, 20 and 40 mg/kg). Significant differences in morphine-induced activation were observed across the panel of AXB/BXA mice. Genetic analysis found significant QTLs on chromosomes 5, 7, 11, 12, 15 and 17 close to loci previously mapped for cocaine-related behaviours and to parameters of dopaminergic functioning (uptake and receptor binding). Comparisons of the A/J vs. C57BL/6J progenitors found no strain differences for total dopamine uptake (V(max) or K(m)) in freshly prepared striatal synaptosomes from naive animals, and no differences in the IC(50) for the inhibition of dopamine uptake by cocaine. In addition, there were no differences in dopamine transporter density (B(max) or K(d)) measured using (3)H-GBR 12935 binding in synaptosomal membranes or via quantitative autoradiography. Multiple-trait analysis was conducted to examine the genetic interrelationships among morphine-, cocaine- and ethanol-induced activation in the AXB/BXA. Analysis yielded suggestive QTLs for the joint trait on chromosomes 5, 8, 13 and 15, as well as significant regions on chromosomes 11 (Pmv46, 11 cM, LOD = 7.39) and 12 (D12Mit110, 19 cM, LOD = 4.43) that may be common to all three drugs of abuse.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".