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Adenosinergic system is involved in development of diazepam tolerance in mice

Joanna Listos1, Sylwia Talarek, Sylwia Fidecka

  • 1Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, 20-081 Lublin, Poland. alistos@op.pl

Pharmacology, Biochemistry, and Behavior
|November 28, 2009
PubMed

Insights

The adenosinergic system influences the development of diazepam tolerance in mice. Adenosine receptor agonists reduced tolerance, while antagonists like caffeine increased it, highlighting the system's role in benzodiazepine tolerance.

Area of Science:

  • Neuropharmacology
  • Behavioral Neuroscience

Background:

  • Benzodiazepine tolerance, particularly to motor impairments caused by diazepam, is a significant clinical concern.
  • The role of the adenosinergic system in modulating drug tolerance is not fully understood.

Purpose of the Study:

  • To investigate the effect of the adenosinergic system on the development of diazepam tolerance to motor disturbances in mice.
  • To determine if adenosine receptor agonists or antagonists can alter diazepam tolerance.

Main Methods:

  • Diazepam tolerance was induced in mice via daily administration for ten days.
  • Motor impairments were assessed using the rota-rod and chimney tests on days 1 and 10.
  • Mice were pretreated with various adenosine receptor agonists (CPA, CGS 21680, NECA) and antagonists (DPCPX, DMPX, caffeine) to evaluate their effects on diazepam tolerance.

Main Results:

  • Acute diazepam administration caused significant motor impairments, which were reduced by repeated treatment, confirming tolerance development.
  • Adenosine receptor agonists (CPA, CGS 21680, NECA) attenuated the development of diazepam tolerance.
  • Adenosine receptor antagonists (DPCPX, DMPX, caffeine) exacerbated diazepam tolerance, with non-selective agents showing the most pronounced effects.

Conclusions:

  • The adenosinergic system plays a crucial role in the mechanisms underlying benzodiazepine tolerance.
  • Modulation of adenosine receptors presents a potential therapeutic target for managing or preventing diazepam tolerance.

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