The Influence Of A1 Adenosine Receptors On Paragigantocellularis Neuronal Firing Rate In Morphine-Dependent Rats

Introduction: Activity of the paragigantocellularis (PGi) nucleus located in the rostral ventrolateral medulla is the mediator of dependence, tolerance and withdrawal syndrome. The most important systems which change their activity during morphine consumption include glutaminergic, opioidergicand purinergic (especially adenosine) receptors in the PGi nucleus. However, it has been shown that the main adaptive changes in the PGi nucleus concerns the adenosine system and especially A1 adenosine receptors.The aim of this study was to investigate whether the different patterns of activity of PGi neurons in tolerance or withdrawal periods could be attributed to adaptive changes in Aladenosine receptors after chronic morphine consumption.
Material and Methods: Animals were allotted randomly to control and dependent groups (in each group n=36). Rats in the dependent group received morphine sulfate in their drinking water for 21 days. The animals were prepared for recording of PGi neuronal firing by micromanipulation of a glassmicropipette into the PGi nucleus near a unit. The unit activity of each neuron was conducted to anextracellular preamplifier and then to an oscilloscope. A window discriminator isolated neuronal firingrate from oscilloscope background activity and the data were recorded and analysed by a PSTH computer program. A1 adenosine receptor agonist and antagonist were administered after a stable recording period (30 min) and the fluctuation of firing rates (spikes/s) was considered as the drug effect.
Results: The spontaneous activity of PGi neurons was significantly decreased by microinjection of the A1 adenosine receptor selective agonist, cyclohexyladenosine (200 µM, Lp), into the PGi nucleus in both control and morphine-dependent rats, but the amount of decrement in morphine-dependent rats(52.5±3.4%) was higher than (P<0.05) that in control rats (35.2±3.1 %).There was also a significant enhancement of spontaneous activity of PGi neurons 10-18 min after the injection of A1 receptor selective antagonist, 8-phenyltheophilline (10 mg/kg; i.p.), in both control and morphine-dependent rats (P<0.05). However, the effect of the antagonist in morphine-dependent rats(39.3±2.5%) was more marked than in control animals (27.2±2.2%). In complementary experiment scyclohexyl adenosine (CHA) was administered in caffeine (50 mg/kg, i.p) pretreated rats. Results show that CHA could not affected PGi neuronal firing rate significantly in both control and dependent rats in this condition.
Conclusion: The data suggest that there was an increase in the sensitivity of A1 adenosine receptors in morphine-dependent rats that may be associated with the PGi neuronal activity patternsduring tolerance and withdrawal syndrome.