UP-REGULATION OF ADENOSINE TRANSPORTER-BINDING SITES IN STRIATUM AND HYPOTHALAMUS OF OPIATE TOLERANT MICE

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 adenosin e uptake and release is regulated by a nitrobenzylthioinosine-sensitiv e 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 [H-3]nitrobenzyl thioinosine in brain regions of morphine-treated mice. A 72-hour morph ine pellet implantation procedure, which previously produced up-regula tion of central adenosine A(1) receptors and created a state of opiate dependence [G.B. Kaplan, K.A. Leite-Morris and M.T. Sears, Alteration s in adenosine A(1) 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%, respectivel y, compared to vehicle pellet implantation. No effects of morphine tre atment were demonstrated in cortex, hippocampus, brainstem or cerebell um. In behavioral studies, mice receiving this same chronic morphine o r vehicle treatment were given saline or morphine injections (40 or 50 mg/kg i.p.) followed by ambulatory activity monitoring. In the chroni c vehicle treatment group, morphine injections significantly stimulate d ambulatory activity while in the chronic morphine group there was no such stimulation by acute morphine, suggestive of opiate tolerance. M orphine-induced up-regulation of striatal and hypothalamic adenosine t ransporter sites could potentially alter extracellular adenosine relea se and adenosine receptor activation and mediate aspects of opiate tol erance and dependence. (C) 1997 Elsevier Science B.V.