Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioural responses in rats

Eur J Pharmacol. 1998 Apr 24;347(2-3):153-8. doi: 10.1016/s0014-2999(98)00107-1.

Abstract

The effects of the systemic (i.p.) administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A receptor agonist sodium 2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS 21680) on different dopamine receptor agonist-induced behaviours were studied in the male rat. CGS 21680 (1 micromol/kg), but not CPA, was found to counteract the stereotypies induced by the non-selective dopamine receptor agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 micromol/kg) and high doses of CPA (3 micromol/kg) counteracted yawning induced by the dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low doses of CPA (0.3 micromol/kg) antagonized grooming induced by the selective dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680 was ineffective. These results are consistent with the proposed existence of a selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1 and A2A receptors, respectively. The ability of CGS 21680 to counteract apomorphine-induced stereotypies is weaker compared to its previously reported antagonistic effect of amphetamine-induced motor activity. This supports the hypothesis that adenosine A2A receptor agonists may be potential antipsychotic drugs with a low potential for extrapyramidal side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects*
  • Dopamine Agonists / pharmacology*
  • Grooming / drug effects
  • Male
  • Phenethylamines / pharmacology*
  • Purinergic P1 Receptor Agonists*
  • Quinpirole / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Purinergic P1 / metabolism
  • Stereotyped Behavior / drug effects
  • Yawning / drug effects

Substances

  • Dopamine Agonists
  • Phenethylamines
  • Purinergic P1 Receptor Agonists
  • Receptor, Adenosine A2A
  • Receptors, Dopamine
  • Receptors, Purinergic P1
  • 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
  • Quinpirole
  • N(6)-cyclopentyladenosine
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Adenosine
  • Apomorphine