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.