Early development of muscarinic supersensitivity in a genetic animal model of depression

L. C. Daws, G. D. Schiller, D. H. Overstreet, J. Orbach

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Adult Flinders-Sensitive Line (FSL) rats are significantly more sensitive to the behavioral and physiologic effects of muscarinic agonists than are control, Flinders-Resistant Line (FRL) rats; therefore, they resemble humans with depressive disorders. The present study examined the sensitivity of prepubertal and pubertal FSL and FRL rats to the hypothermic and locomotor inhibitory effects of the muscarinic agonist, oxotremorine, and compared these findings to the regional development of muscarinic receptor binding in similarly aged rats. The FSL rats were significantly more sensitive (-1.85° ± 0.2°C) than the FRL rats (-0.65° ± 0.15°C) to the hypothermic effect of 0.25 μmol/kg of oxotremorine at the earliest age tested (18 days postpartum) and became progressively more sensitive throughout the period of testing (FSL -2.8° ± 0.24°C versus FRL -0.5° ± 0.16°C at 61 days postpartum, data represent the mean ± SEM of pooled male and female). Significant increases in muscarinic receptor number in FSL rat brain were observed only in older (61 days postpartum) rats. These results are consistent with the suggestion that the FSL rat is a genetic animal model of depression, but also indicate that the difference in muscarinic sensitivity cannot be accounted for exclusively by differences in the number, per se, of muscarinic receptors.

Original languageEnglish (US)
Pages (from-to)207-217
Number of pages11
JournalNeuropsychopharmacology
Volume4
Issue number3
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • Acetylcholine
  • Child development
  • Depressive disorder
  • Disease models, animals
  • Models, genetic
  • Muscarinic receptors
  • Oxotremorine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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