Abstract
The hypotensive actions of morphine have been shown to be mediated by adenosine. Since tolerance has been reported to the hypotensive effects of morphine, this study was designed to determine whether morphine dependence altered adenosine receptor-mediated decreases in blood pressure in the Hooded Wistar rat. Following the induction of morphine dependence, the effects of adenosine receptor agonists and antagonists were studied in intact and pithed rat preparations. The hypotensive effects of adenosine were significantly less in morphine-dependent rats when compared to opiate naive rats. The adenosine A 1 receptor agonist cyclohexyladenosine induced decreases in diastolic blood pressure which were significantly reduced in morphine-dependent rats when compared to opiate naive rats. However, the adenosine A 2 a receptor agonist 2- p-(car☐yethyl)-phenylamino-5′- N-ethylcar☐amidoadenosine (CGS 21680) had a greater effect on blood pressure in morphine-dependent rats compared to opiate naive rats. The effects of adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, 8-phenyltheophylline, 8-( p-sulfophenyl)theophylline and 3,7-dimethyl-1-propargylxanthine infused at 50 μg/kg per min on the hypotensive actions of adenosine were studied in opiate naive and morphine-dependent rats. In intact rats the induction of morphine dependence reduced the potency of these antagonists at inhibiting adenosine-induced decreases in blood pressure. The same series of experiments was conducted in the pithed rat preparation. In this case the hypotensive actions of both cyclohexyiadenosine and CGS 21680 were greater in morphine-dependent rats than opiate naive rats. In pithed rats, morphine dependence did not change the potencies of adenosine receptor antagonists on he hypotensive actions of adenosine. These results suggest that adenosine A 1 receptors are downregulated in morphine-dependent rats, and that adenosine A 2 receptors are upregulated in morphine-dependent rats.
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