Literature DB >> 2740431

MR/Har and MNRA/Har Maudsley rat strains: differential response to chlordiazepoxide in a conflict task.

R L Commissaris1, T C McCloskey, G M Harrington, H J Altman.   

Abstract

The Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains, selectively bred for differences in open field defecation, have also been shown to differ in their baseline behavior in the Conditioned Suppression of Drinking (CSD) procedure, a second "model" behavior for the study of anxiety and/or emotionality in rats. The present studies were designed to compare the responsiveness of these two strains to the typical antianxiety agent chlordiazepoxide in the CSD paradigm. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube that was occasionally electrified (0.5 mA), electrification being signaled by a tone. Consistent with previous reports, after several weeks of CSD testing, MNRA/Har rats accepted significantly more shocks than did MR/Har rats during control (nondrug) sessions. In both strains, the number of shocks accepted was inversely related to the intensity of the shock used (0.25-1.0 mA), with MNRA/Har rats accepting significantly more shocks than MR/Har rats at all intensities examined. The effects of various doses (1.25-28.4 mg/kg, IP) of chlordiazepoxide were determined in subjects of the MNRA/Har strain at the original training intensity (0.5 mA), while a lower intensity (0.25 mA) was utilized in MR/Har rats. Although punished responding in control (i.e., nondrug) CSD sessions did not differ under these conditions, MNRA/Har rats were found to be more responsive to the anticonflict effects of chlordiazepoxide than rats of the MR/Har strain. This strain difference in anticonflict efficacy of chlordiazepoxide was quite dramatic, with MNRA/Har rats accepting twice as many shocks as MR/Har rats following maximally effective doses of chlordiazepoxide. Low doses of chlordiazepoxide increased water intake slightly, while higher doses decreased water intake. Surprisingly, the chlordiazepoxide-induced depression of water intake was greater in rats of the MR/Har strain. Thus, these Maudsley Reactive and Non-Reactive rat strains, bred originally for their differences in open field behavior, also differ markedly in their responsiveness to chlordiazepoxide in the CSD paradigm. These findings further support the hypothesis that the MR/Har and MNRAHar rat strains may represent a genetically-based "animal model" for the study of emotionality and/or anxiety.

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Year:  1989        PMID: 2740431     DOI: 10.1016/0091-3057(89)90037-3

Source DB:  PubMed          Journal:  Pharmacol Biochem Behav        ISSN: 0091-3057            Impact factor:   3.533


  5 in total

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Authors:  A Fernández-Teruel; R M Escorihuela; A Tobeña; P Driscoll
Journal:  Experientia       Date:  1991-10-15

Review 2.  The age of anxiety: role of animal models of anxiolytic action in drug discovery.

Authors:  John F Cryan; Fabian F Sweeney
Journal:  Br J Pharmacol       Date:  2011-10       Impact factor: 8.739

Review 3.  50 years of hurdles and hope in anxiolytic drug discovery.

Authors:  Guy Griebel; Andrew Holmes
Journal:  Nat Rev Drug Discov       Date:  2013-09       Impact factor: 84.694

4.  Benzodiazepine anti-conflict effects in Maudsley reactive (MR/Har) and non-reactive (MNRA/Har) rats.

Authors:  R L Commissaris; G M Harrington; H J Altman
Journal:  Psychopharmacology (Berl)       Date:  1990       Impact factor: 4.530

5.  Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type.

Authors:  A M Perkins; U Ettinger; K Weaver; A Schmechtig; A Schrantee; P D Morrison; A Sapara; V Kumari; S C R Williams; P J Corr
Journal:  Transl Psychiatry       Date:  2013-04-16       Impact factor: 6.222

  5 in total

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