Pharmacological Blockade of Serotonin 5-HT7 Receptor Reverses Working Memory Deficits in Rats by Normalizing Cortical Glutamate Neurotransmission
2011

5-HT7 Antagonist Reverses Cognitive Deficit in Rats

Sample size: 6 publication Evidence: moderate

Author Information

Author(s): Bonaventure Pascal, Aluisio Leah, Shoblock James, Jamin D. Fraser, Ian C. Lord, Brian Lovenberg, Timothy W. Galici, Ruggero Johnson

Primary Institution: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.

Hypothesis

Can the selective 5-HT7 antagonist SB-269970 improve working memory deficits in rats by modulating cortical glutamate and dopamine neurotransmission?

Conclusion

The study found that the 5-HT7 receptor antagonist SB-269970 reversed cognitive deficits induced by MK-801 but not those induced by scopolamine.

Supporting Evidence

  • SB-269970 significantly reversed MK-801-induced cognitive deficits in the delayed non-matching to position task.
  • SB-269970 did not affect dopamine levels but normalized glutamate levels in the prefrontal cortex.
  • The pharmacokinetic study showed that SB-269970 did not alter the plasma and brain concentrations of MK-801.

Takeaway

Researchers tested a drug on rats to see if it could help them remember things better, and it worked for some types of memory problems but not others.

Methodology

The effects of SB-269970 were evaluated in a delayed non-matching to position task and its impact on glutamate and dopamine levels was measured using biosensor technology and microdialysis.

Potential Biases

Potential conflicts of interest due to funding from Johnson & Johnson Pharmaceutical Research and Development.

Limitations

The study's findings may not be generalizable to all types of cognitive deficits or other species.

Participant Demographics

Male Sprague-Dawley rats, weighing 250-350 grams.

Statistical Information

P-Value

p<0.00005

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0020210

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