Acute kappa opioid receptor blocking disrupts the pro-cognitive effect of cannabidiol in neuropathic rats
Bibliographic record
Abstract
Cannabidiol has been shown to ameliorate neuropathic pain and its affective components. Previous studies highlighted the pharmacological interaction between the CBD and opioid system, particularly the MOR, but the understanding of the interaction between CBD and kappa opioid receptor (KOR), physiologically stimulated by the endogenous opioid dynorphin, remains elusive. We assessed the pharmacological interactions between CBD and nor-BNI, a selective KOR antagonist in a rat neuropathic pain model. We show an increase in dynorphin peptide and its KOR receptors in the hippocampus’ dentate gyrus (DG) of neuropathic rats showing allodynia, and memory deficits. Consistent with these findings, neuropathic pain was associated with long-term potentiation (LTP) impairment in the entorhinal cortex-DG, also referred to as the lateral perforant pathway (LPP). Moreover, a downregulation of the endocannabinoid 2-AG and an upregulation of the cannabinoid CB1 receptors in the DG were detected in neuropathic pain animals. Either an acute KOR antagonist administration or one-week CBD treatment normalized dynorphin levels and improved affective symptoms, LTP and receptor expression, whereas only CBD showed an anti-allodynic effect. In addition, CBD normalized the SNI-induced changes in neuroplasticity as well as endocannabinoid and GABA levels in the DG. Noteworthy, the acute blockade of the KOR carried out after CBD repeated administration causes the re-installment of some neuropathic condition symptoms. As a whole, these original results indicate a critical relationship between the adaptive changes in the hippocampus produced by CBD and the need to maintain the recovered physiological dynorphin tone to preserve the therapeutic effect of CBD in neuropathic rats. • SNI induces neuroplasticity disruption and changes in CB1 or KOR levels in the DG • CBD normalizes synaptic plasticity and endocannabinoid and GABA levels in SNI rats • KOR antagonism normalizes dynorphin levels, synaptic plasticity and receptor expression • KOR blockade abolishes the pro-cognitive effect induced by CBD in SNI rats • Dynorphin tone controls the neuroprotective effect of CBD in neuropathic rats
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".