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Related Experiment Videos

Enhanced benzodiazepine responsiveness in rats with increased cholinergic function.

S Pepe1, D H Overstreet, A D Crocker

  • 1Department of Clinical Pharmacology, School of Medicine, Flinders University of South Australia.

Pharmacology, Biochemistry, and Behavior
|September 1, 1988
PubMed
Summary

Flinders Sensitive Line (FSL) rats exhibit heightened sensitivity to diazepam and muscimol. This increased behavioral response is linked to a higher concentration of benzodiazepine receptors in their striatum and hippocampus.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Genetics

Background:

  • Flinders Sensitive Line (FSL) rats are selectively bred for heightened sensitivity to anticholinesterase agents.
  • Previous studies indicate FSL rats have increased muscarinic receptor concentrations and sensitivity to oxotremorine.
  • Benzodiazepine and GABAergic systems are crucial in regulating locomotor activity.

Purpose of the Study:

  • To investigate the effects of diazepam and muscimol on locomotor activity in FSL rats.
  • To compare the sensitivity and benzodiazepine receptor binding characteristics of FSL rats with randomly bred (RB) and Flinders Resistant Line (FRL) rats.
  • To elucidate the neurobiological underpinnings of altered drug sensitivity in FSL rats.

Main Methods:

  • Locomotor activity tests were conducted on FSL, FRL, and RB rats following administration of diazepam and muscimol.

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  • Radioligand binding assays using [3H]-diazepam were performed to quantify benzodiazepine receptor concentrations in specific brain regions.
  • Behavioral sensitivity and receptor binding data were statistically analyzed and compared across rat lines.

    • Main Results:

    • FSL rats demonstrated significantly greater sensitivity to the locomotor suppressant effects of both diazepam and muscimol compared to RB rats.
    • Binding experiments revealed a higher concentration of benzodiazepine receptors in the striatum and hippocampus of FSL rats relative to FRL rats.
    • No significant differences in benzodiazepine receptor affinity were observed among the three rat lines.

    Conclusions:

    • FSL rats exhibit enhanced behavioral sensitivity to diazepam and muscimol, suggesting alterations in GABAergic neurotransmission.
    • The increased sensitivity is associated with a higher density of benzodiazepine receptors in key brain areas like the striatum and hippocampus.
    • FSL rats serve as a valuable model for studying the neurobiological basis of differential drug responses and benzodiazepine receptor function.