No evidence for cross-talk between the adenosine A1 and the serotonin-1A receptor system after chronic A1 receptor stimulation

Several studies show that different neurotransmitter receptor systems may interact with each other, for example, by means of a shared pool of G-proteins coupled to these receptors. Along these lines, there are data suggesting cross-talk between the adenosine and serotonin receptor systems. Such an interaction between these two receptor systems may also emerge under conditions of sleep loss which is characterized by increased adenosine turn over. In the present study, we tested whether chronic application of the adenosine A1 receptor agonist N-cyclopentyladenosine (CPA) not only desensitizes the adenosine receptors but also affects serotonin-1A signalling. The present study shows that chronic injections with CPA caused a decrease in adenosine A1 receptor numbers and an increase in the amount of adenosine A1 receptor-activated G-proteins in a region specific manner. On the level of physiological output, that is, CPA-induced and A1 receptormediated hypothermia, we found a reduced temperature response suggesting a desensitization of the receptor system. Nevertheless, the hypothermic response to the serotonin-1A receptor agonist 8-OH-DPAT was not altered in these animals, indicating that there had not been crossdesensitization of the response. In conclusion, the present study shows that chronic application of the A1 agonist CPA desensitizes the adenosine A1 receptor system but it does not alter serotonin1A receptor-associated signalling as measured by the functional hypothermic response.