Catecholaminergic activity and 3 ',5 '-cyclic adenosine monophosphate concentrations in the right ventricle after acute and chronic morphine administration in the rat

We have examined possible regulation of norepinephrine and dopamine concent rations and turnover in the right ventricle of the rat after acute administ ration of saline i.p. or morphine 30 mg kg(-1) i.p. to placebo (naive) or m orphine (tolerant) pretreated rats. We also assessed concentrations of 3',5 '-cyclic adenosine monophosphate (cAMP) in the right: ventricle after the s ame treatments. Concentrations of catecholamines and their metabolites in t he heart were measured by high-pressure liquid chromatography with electroc hemical detection (HPLC/DE). Concentrations of cAMP in the heart were measu red by radioimmunoassay (RIA), Administration of morphine to naive rats did not modify concentrations of norepinephrine (NE), normetanephrine (NMN) or NMN/NE ratio in the right: ventricle. However, dopamine concentrations inc reased whereas dopamine turnover decreased. In addition, cAMP concentration s decreased after acute administration morphine to naive rats. In rats pret reated with morphine chronically, there was an increase in norepinephrine c oncentrations with no change in normetanephrine concentrations or norepinep hrine turnover after acute injection of morphine. In contrast, dopamine tur nover increased in the tolerant groups after acute injection of saline or m orphine compared with the naive group given morphine, indicating that toler ance develops to the acute effects of the opioid. Concentrations of cAMP in creased after chronic morphine administration. Our results demonstrate that chronic morphine pretreatment leads to up-regulation of the cAMP system in the heart and suggest that this up-regulation may be involved in the cellu lar mechanisms implicated in the adaptive changes of dopaminergic neurones in the heart observed during chronic treatment with morphine.