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5-HT(1A) Receptor Null Mutant Mice Responding Under a Differential-Reinforcement-of-Low-Rate 72-Second Schedule of
Jonah J Scott-McKean1, Galen R Wenger, Laurence H Tecott
1Neuroscience Training Program, University of Colorado Denver, Aurora, CO, USA.
The Open Neuropsychopharmacology Journal
|March 31, 2010
Summary
This study validates the differential-reinforcement-of-low-rates 72-second (DRL 72-s) operant schedule as a mouse model for antidepressant action. It shows fluoxetine and desipramine effects in genetically modified and wild-type mice, mirroring rat model findings.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Genetics
Background:
- Genetically engineered mouse models are crucial for studying depression and neurological disorders.
- Some validated rodent models for depression, like the DRL 72-s operant schedule, exist only in rats.
- The DRL 72-s schedule in rats predicts antidepressant activity based on drug-induced performance changes.
Purpose of the Study:
- To validate the differential-reinforcement-of-low-rates 72-second (DRL 72-s) operant schedule as a behavioral model in mice.
- To assess antidepressant actions using genetic and pharmacological strategies in mice.
Main Methods:
- Administered fluoxetine (SSRI) and desipramine (DMI) to wild-type (Wt) and 5-hydroxytryptamine 1A receptor-null mutant (5-HT(1A)R KO) mice.
- Analyzed drug effects on performance within the DRL 72-s operant schedule.
- Utilized genetic manipulation (5-HT(1A)R KO) and pharmacological agents for validation.
Main Results:
- Fluoxetine demonstrated an antidepressant-like effect in 5-HT(1A)R KO mice, but not in Wt mice, consistent with rat studies.
- Desipramine produced an antidepressant-like effect in both Wt and 5-HT(1A)R KO mice.
- Findings confirm specific drug-induced behavioral changes predict antidepressant activity in mice.
Conclusions:
- The DRL 72-s operant schedule is validated as a behavioral model for antidepressant action in mice.
- This study successfully extends the utility of the DRL 72-s protocol to mouse models using genetic and pharmacological approaches.
- The findings support the use of this mouse model for preclinical screening of antidepressant drugs.
