Kissorphin improves spatial memory and cognitive flexibility impairment induced by ethanol treatment in the Barnes maze task in rats.
Gibula-Tarlowska. Ewa E; Kotlinska. Jolanta H JH
Key Findings
- Kissorphin (10 nmol i.v.) prevented spatial memory loss and improved reversal learning in rats given a high dose of ethanol.
- When given during ethanol withdrawal, kissorphin reduced deficits in cognitive flexibility in the Barnes maze.
- The protective effects were dose‑dependent, with the 10 nmol dose being most effective in both acute and chronic alcohol models.
Practical Outcomes
- For now, the results are only in rats, so there’s no direct protocol you can apply. The study does hint that targeting the endogenous opioid system could be a strategy for mitigating alcohol‑related cognitive issues, but human safety, dosing, and efficacy remain unknown. Biohackers should wait for human trials before considering any kisspeptin‑derived supplements for this purpose.
Summary
In rats, a new peptide called kissorphin (based on kisspeptin-10) helped protect against memory problems caused by alcohol exposure and withdrawal. The biggest benefit was seen at the highest dose tested (10 nmol). The study suggests that tweaking the brain's opioid system might reverse alcohol‑related learning deficits, but it’s all animal work and not yet ready for human use.
Abstract
Acute and chronic ethanol intake, as well as ethanol withdrawal, exert learning disabilities. Of all the neurotransmitters in the brain, endogenous opioid peptides are thought to participate in ethanol effects. Kisspeptins, including kisspeptin-10, are peptides produced in the part of brain involved in the consolidation of memory and orientation. A new derivative of kisspeptin-10 is kissorphin (Tyr-Asn-Trp-Asn-Ser-Phe-NH2), a peptide with anti-opioid-activity. Hence, the aim of our study was to reveal whether kissorphin (1, 3, and 10 nmol, i.v.) was able to prevent or reverse learning deficits such as spatial memory retention and reversal learning induced by acute ethanol administration (1 × 1.75 g/kg., i.p.) and reversal learning induced by ethanol withdrawal (11-13 days from 'binge-like' ethanol input-5.0 g/kg, i.g. for 5 days) in the Barnes maze task in rats. Our study demonstrated that acute kissorphin administration prevented spatial memory (higher doses) impairments and attenuated reversal learning deficits induced by acute ethanol administration, although the reversal learning impairment may have been due to spatial learning impairments rather than cognitive flexibility impairments. Moreover, kissorphin given prior to first reversal learning trial for 3 consecutive days in the Barnes maze task during withdrawal from 'binge-like' ethanol administration, significantly attenuated cognitive flexibility impairment in the ethanol-withdrawal rats. In the acute and chronic ethanol experiments, kissorphin was the most effective at the dose of 10 nmol. In conclusion, the ethanol-induced spatial memory impairment may be reversed by pharmacological manipulation of the endogenous opioid system.
Study Information
pubmed
2020
10.1097/fbp.0000000000000557