Alterations of adenosine A1 receptors in morphine dependence.
The possibility that central adenosine A1 and A2a receptors mediate opiate dependence was examined in morphine-treated mice using radioligand binding methods. Mice treated with morphine for 72 h demonstrated significant increases in naloxone precipitated abstinence behaviors of jumping, wet-dog shakes, teeth chattering, forepaw trends, forepaw tremors and diarrhea compared to vehicle-treated mice. Increased concentrations of cortical adenosine A1 receptor sites, but not striatal adenosine A2a sites, were found in saturation binding studies from morphine-dependent mice. Decreases in cortical A1 agonist binding affinity values along with increases in agonist binding sites were demonstrated in competition binding studies. These results suggest that adaptive changes of upregulation and sensitization of adenosine A1 receptors play a role in mediating the opiate abstinence syndrome.
Kaplan
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GB
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02908-4799.
Leite-Morris
K A
KA
Sears
M T
MT
D000818:Animals; D001667:Binding, Competitive; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D011869:Radioligand Assay; D018047:Receptors, Purinergic P1 / Q000378:metabolism / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D018047:Receptors, Purinergic P1