Modulation of adenosine concentration by opioid receptor agonists in rat striatum

There is evidence that adenosine and morphine interact in the striatum. How ever, little is known about the precise role of the opioid receptor subtype s implicated in the modulation of adenosine tissue concentration and in ade nosine receptor expression and function. We sought to evaluate, in the abse nce of withdrawal symptoms, the effects of the short-term administration of selective mu-, delta- or kappa-opioid receptor agonists on adenosine conce ntration and on adenosine A(2A) receptor function in rat striatum. Adenosin e A(2A) receptor was chosen because the neuronal sub-population expressing this receptor coexpresses enkephalin, suggesting that adenosine A(2A) recep tor may be regulated by opioid receptor agonists. Oxymorphone hydrochloride (mu-opioid receptor agonist, 6 mg/kg/day), +[-(5 alpha,7 alpha,8 beta)-(-) -N-methyl-N(7-(1-pyrrolidinyl)1-oxaspiro (4.5)dec-8-yl) benzenacetamide] (U 69593) (kappa-opioid receptor agonist, 0.75 mg/kg/day), and (+)-4[(alpha R) -alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-di ethylbenzamide) (SNC80) (delta-opioid receptor agonist, 9 mm/kg/day), or ve hicle, were administered i.p 3 x daily during 5 days to groups of rats (n = 6). We also investigated the effects of opioid receptor agonists on adenos ine uptake by striatal cell extracts. We found that administration of mu- o r delta-opioid receptor agonists significantly decreased adenosine uptake i n striatal cell extracts and increased adenosine concentration (mean +24% a nd +45% for mu- and delta-opioid receptor agonist, respectively, relative t o controls). None of the receptor agonists tested induced obvious modificat ions of adenosine A(2A) receptor function. However, the delta-opioid recept or agonist induced an increase in adenosine A(2A) mRNA expression (mean 44% ). We conclude that mu and delta receptor agonists inhibit adenosine uptake by striatal cell extracts and increase adenosine concentrations in rat str iatum. (C) 2000 Elsevier Science B.V, All rights reserved.