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Related Experiment Videos

Adenosine agonists reduce conditioned avoidance responding in the rat

G E Martin1, D J Rossi, M F Jarvis

  • 1Department of Pharmacology, Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426.

Pharmacology, Biochemistry, and Behavior
|August 1, 1993
PubMed
Summary
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Adenosine agonists show potential as antipsychotic agents by blocking conditioned avoidance responding in rats. The nonselective agonist NECA was the most potent, suggesting purinergic receptor involvement.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Adenosine agonists are being investigated for their potential therapeutic applications as antipsychotic agents.
  • Conditioned avoidance responding (CAR) in rats is a validated behavioral test predictive of antipsychotic efficacy in humans.
  • Schizophrenia treatment efficacy is directly proportional to an agent's potency in blocking CAR.

Purpose of the Study:

  • To evaluate the in vivo activity of various adenosine agonists in blocking CAR in rats.
  • To compare the potency of selective A1 and A2 adenosine agonists, as well as a nonselective agonist, in the CAR test.
  • To explore the role of purinergic receptors in mediating the observed behavioral effects.

Main Methods:

  • Adenosine agonists (NECA, R-PIA, CGS 21680, CV-1808, CPA) were administered to rats.

Related Experiment Videos

  • The ability of these agonists to block CAR, a light- and tone-signaled footshock avoidance task, was assessed.
  • Standard antipsychotic agents (haloperidol, trifluoroperazine, etc.) were used as benchmarks.
  • Adenosine receptor binding affinities were determined in rat brain tissue.
  • The effect of caffeine pretreatment on agonist-induced CAR blockade was examined.

    • Main Results:

    • All tested adenosine agonists effectively blocked CAR in rats.
    • The nonselective agonist NECA demonstrated the highest potency (ED50 = 0.07 mg/kg), followed by R-PIA, CGS 21680, CV-1808, and CPA.
    • Adenosine agonist potencies in blocking CAR were determined.
    • Caffeine pretreatment antagonized the CAR blocking effects of adenosine agonists, supporting a purinergic mechanism.

    Conclusions:

    • Adenosine agonists exhibit significant antipsychotic-like activity in the CAR model.
    • The nonselective adenosine agonist NECA is particularly potent in this behavioral assay.
    • The findings suggest that targeting purinergic receptors may be a viable strategy for developing novel antipsychotic medications.