ALTERATIONS OF ADENOSINE A(1) RECEPTORS IN MORPHINE-DEPENDENCE

The possibility that central adenosine A(1) and A(2a) receptors mediat e opiate dependence was examined in morphine-treated mice using radiol igand binding methods. Mice treated with morphine for 72 h demonstrate d significant increases in naloxone-precipitated abstinence behaviors of jumping, wet-dog shakes, teeth chattering, forepaw treads, forepaw tremors and diarrhea compared to vehicle-treated mice. Increased conce ntrations of cortical adenosine A(1) receptor sites, but not striatal adenosine A(2a) sites, were found in saturation binding studies from m orphine-dependent mice. Decreases in cortical A(1) agonist binding aff inity values along with increases in agonist binding sites were demons trated in competition binding studies. These results suggest that adap tive changes of upregulation and sensitization of adenosine A(1) recep tors play a role in mediating the opiate abstinence syndrome.