An increase in opiate receptor-sites is associated with enhanced cardiovascular depressant, but not respiratory depressant action of morphine.

Rats were treated for 4 weeks with a constant infusion of 2 mg/kg/h of the opiate antagonist naloxone. This treatment increased mu-, delta- and kappa-binding sites by 60-180% in several brain regions, suggesting effective blockade of the 3 types of opiate sites. The significance of changes in opiate binding sites for opiate receptor mediated physiological responses were examined using cardiovascular and respiratory responses to morphine (assessed after elimination of naloxone) as physiological parameters. Chronically naloxone-treated rats showed no alteration in respiratory responses to morphine, whereas there was a marked supersensitivity to depressor and bradycardic effects and a loss of pressor and tachycardic effects of morphine. These data are the first indication that cardiovascular effects of opiates vary with changes in central opiate receptor levels. Our observations, moreover, show that there are complex relationships between receptor number and receptor-mediated effects of opiates.