Intra- and interstrain differences in models of "behavioral despair".

Area of Science:

• Neuroscience
• Behavioral Pharmacology
• Animal Models

Background:

• The forced swim test (FST) and tail suspension test (TST) are widely used to assess antidepressant-like behavior in rodents.
• Understanding the neurobiological underpinnings of these tests is crucial for accurate interpretation of results.

Purpose of the Study:

• To compare baseline and drug-induced performance in the FST and TST across two mouse strains (C57Bl/6 and NIH-Swiss).
• To investigate potential differences in the biological substrates mediating performance in these two behavioral tests.

Main Methods:

• Evaluation of baseline immobility in C57Bl/6 and NIH-Swiss mice using FST and TST.
• Assessment of drug effects (imipramine and LY451646) on behavior in FST and TST.
• Intra- and interstrain comparisons of behavioral responses.

Main Results:

• Significant differences in baseline immobility were observed between FST and TST in NIH-Swiss mice, but not in C57Bl/6 mice.
• Imipramine exhibited a "U-shaped" dose-response curve in the FST for C57Bl/6 mice, but not in the TST.
• The AMPA receptor potentiator LY451646 showed strain-dependent potency differences in the FST, influenced by pharmacokinetic and pharmacodynamic factors.

Conclusions:

• The neurochemical pathways underlying performance in the FST and TST are not identical.
• Strain-specific differences in behavioral responses suggest distinct biological substrates for each test.
• These findings challenge the assumption of interchangeable utility between FST and TST in behavioral pharmacology.