Gb. Kaplan et Ka. Leitemorris, UP-REGULATION OF ADENOSINE TRANSPORTER-BINDING SITES IN STRIATUM AND HYPOTHALAMUS OF OPIATE TOLERANT MICE, Brain research, 763(2), 1997, pp. 215-220
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.