Adenosine A2 receptors inhibit morphine self-administration in rats
Introduction
Adenosine is an important neuromodulator in the central nervous system (CNS) (Dunwiddie, 1985). Specific receptor sites for adenosine have been demonstrated within the areas of the CNS (Lee and Reddington, 1986). A great number of research findings indicate that adenosine receptors have a role in mediating opiate effects (Kaplan and Sears, 1996). Acute morphine treatment enhances the central release of adenosine, and opiate antagonist inhibits this release (Phillis et al., 1979). Adenosine receptor agonist treatment may alter (Zarrindast and Nikfar, 1994), or even potentiate morphine antinociception in animal models (Contreras et al., 1990) and in humans (Segerdhal et al., 1994). There are several studies that demonstrate that adenosine receptor agonists and antagonists influence the development of opiate tolerance and withdrawal. Some adenosine receptor agonists inhibit the development of tolerance to opiate analgesia Ahlijanian and Takemori, 1985, Germany et al., 1990, and expression of opiate withdrawal Tucker et al., 1984, Dionyssopoulos et al., 1992. The adenosine system has also been implicated in conditioned place preference (Zarrindast and Moghadamnia, 1997), however, there is little evidence for possible effects of the adenosine system on morphine self-administration. In this study the influence of some adenosine receptor agonists and antagonists on morphine self-administration was investigated.
Section snippets
Animals
Male Sprague–Dawley rats (Pasture Institute, Tehran, Iran), weighing 270–320 g at the beginning of the study were used in these experiments. The animals were housed in groups of 5–6 in plastic cages, allowed free access to food and water and maintained on a 12-h light–dark cycle (lights on 1900–0700) and constant temperature (22±2°C). Eight animals were used in each experiment. Each animal was used only once.
Surgical procedure
The surgical procedure was based on the work described by Van Ree et al. (1978). Each
Self-administration behavior with morphine and adenosine receptor agonists and antagonists
Fig. 1 shows the self-administration induced by morphine, NECA, CGS21680, theophylline and DMPX. When rats were given the opportunity to self-administer, the number of saline self-administrations was 1–3 injections, after a period of training (a unit volume of 0.1 ml=one injection). In contrast, the animals which were given the opportunity to self-administer different doses of morphine (0.3–3 mg/kg/injection) in a period of 2 h, achieved self-administration in a dose-dependent manner. The
Discussion
The effect of the adenosine system on morphine self-administration has not been studied earlier. Many studies have described a role for adenosine and adenosine receptors in mediating opiate dependence Ahlijanian and Takemori, 1985, Ahlijanian and Takemori, 1986, Kaplan and Sears, 1996. The present study concerned the effects of adenosine agents on morphine self-administration. The results indicated that adenosine receptor agonists and antagonists both alter morphine self-administration,
References (36)
- et al.
Effects of (−)-N6(R-Phenylisopropyl)-adenosine (PIA) and caffeine on nociception and morphine-induced analgesia, tolerance and dependence in mice
Eur. J. Pharmacol.
(1985) - et al.
Decreased adenosine A2 receptor function in morphine dependent rats
Pharmacol. Res.
(1992) - et al.
Effect of adenosine analogues on the expression of opiate withdrawal in rats
Pharmacol. Biochem. Behav.
(1992) The physiological role of adenosine in the central nervous system
Int. Rev. Neurobiol.
(1985)- et al.
Postsynaptic dopamine/adenosine interaction: II. Postsynaptic dopamine agonism and adenosine antagonism of methylxanthines in short-term reserpinized mice
Eur. J. Pharmacol.
(1991) - et al.
Adenosine-dopamine interactions in the brain
Neuroscience
(1992) - et al.
Alterations of adenosine A1 receptors in morphine dependence
Brain Res.
(1994) - et al.
Autoradiographic evidence for multiple CNS binding sites for adenosine derivatives
Neuroscience
(1986) - et al.
3,7-Dimethyl-1-1-propargylxantine: a potent and selective in vivo antagonist of adenosine analogues
Life Sci.
(1988) - et al.
Chronic morphine treatment causes downregulation of spinal adenosine A1 receptors in rats
Eur. J. Pharmacol.
(1992)