Opioid-
adenosine interactions have been demonstrated at both cellular and behavioral levels. Short-term
morphine treatment has been shown to enhance
adenosine release in brain and spinal tissues. Since
adenosine uptake and release is regulated by a nitrobenzylthioinosine-sensitive
adenosine transporter, we examined the effects of
morphine treatment on this transporter-binding site.
Adenosine transporter-binding sites were examined using equilibrium binding studies with [3H]nitrobenzylthioinosine in brain regions of
morphine-treated mice. A 72-hour
morphine pellet implantation procedure, which previously produced up-regulation of central
adenosine A1 receptors and created a state of
opiate dependence [G.B. Kaplan, K.A. Leite-Morris and M.T. Sears, Alterations in
adenosine A receptors in
morphine dependence, Brain Res., 657 (1994) 347-350], was used in this current study. This chronic
morphine treatment significantly increased
adenosine transporter-binding site concentrations in striatum and hypothalamus by 12 and 37%, respectively, compared to vehicle pellet implantation. No effects of
morphine treatment were demonstrated in cortex, hippocampus, brainstem or cerebellum. In behavioral studies, mice receiving this same chronic
morphine or vehicle treatment were given saline or
morphine injections (40 or 50 mg/kg i.p.) followed by ambulatory activity monitoring. In the chronic vehicle treatment group,
morphine injections significantly stimulated ambulatory activity while in the chronic
morphine treatment group there was no such stimulation by acute
morphine, suggestive of
opiate tolerance.
Morphine-induced up-regulation of striatal and hypothalamic
adenosine transporter sites could potentially alter extracellular
adenosine release and
adenosine receptor activation and mediate aspects of
opiate tolerance and dependence.