Intra- and interstrain differences in models of "behavioral despair".
In the present studies, base line and drug-induced performance of two mouse strains (C57Bl/6 and NIH-Swiss) was evaluated in the forced swim test (FST) and tail suspension test (TST). Intra- and interstrain comparisons indicate that the biological substrates mediating performance in these behavioral procedures are not identical. For example, in NIH-Swiss mice, a sevenfold difference in base line immobility was observed between the FST and TST. By contrast, the base line immobility in C57Bl/6 mice was similar in both procedures. Further, in C57Bl/6 mice, imipramine produced a "U-shaped" dose-response curve in the FST, whilst no evidence of a biphasic response was present in the TST at doses up to 45 mg/kg. In the FST, the AMPA receptor potentiator LY451646 produced a similar dose-response relationship in C57Bl/6 and NIH-Swiss mice, but the minimum effect dose (MED) was fivefold higher in NIH-Swiss mice. This potency difference appears due to both pharmacokinetic and pharmacodynamic factors. These intra- and interstrain differences in performance indicate that despite a face value similarity, the neurochemical pathways involved in mediating performance in these two widely used tests are not identical.
Bai
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Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, DC 0510, Indianapolis, IN 46285-0510, USA. bai_fengju@lilly.com
Li
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Clay
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Lindstrom
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Skolnick
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P
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018091:Receptors, AMPA / Q000819:agonists; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D018690:Excitatory Amino Acid Agonists; C430915:LY 404187; D018091:Receptors, AMPA; D013449:Sulfonamides; D007099:Imipramine