Related Experiment Videos
Alterations of adenosine A1 receptors in morphine dependence
G B Kaplan1, K A Leite-Morris, M T Sears
1Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02908-4799.
Abstract:
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.
Insights
Central adenosine A1 receptors, but not A2a receptors, are upregulated in morphine-dependent mice. This suggests adenosine A1 receptor changes mediate opiate withdrawal symptoms.
Area of Science:
- Neuroscience
- Pharmacology
- Receptor Biology
Background:
- Opiate dependence is a significant public health concern.
- The role of central adenosine receptors in opiate dependence is not fully understood.
Purpose of the Study:
- To investigate the involvement of central adenosine A1 and A2a receptors in mediating opiate dependence.
- To examine adaptive changes in adenosine receptor function during morphine treatment.
Main Methods:
- Radioligand binding assays were used to quantify adenosine A1 and A2a receptor sites and affinities in the brains of morphine-treated mice.
- Behavioral assessments were conducted to evaluate naloxone-precipitated abstinence symptoms.
Main Results:
- Morphine treatment for 72 hours induced significant opiate abstinence behaviors.
- Increased concentrations of cortical adenosine A1 receptor sites were observed in morphine-dependent mice.
- Decreased A1 agonist binding affinity and increased agonist binding sites in the cortex suggest receptor upregulation and sensitization.
Conclusions:
- Adaptive changes, specifically upregulation and sensitization, of cortical adenosine A1 receptors play a role in mediating the opiate abstinence syndrome.
- Adenosine A1 receptors are implicated in the neurobiological mechanisms underlying opiate dependence and withdrawal.