Effects of the putative 5-HT 1A receptor agonist 8-OH-2-(di-n-propylamino)tetralin on nociceptive sensitivity in mice

Abstract

The ability of 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT) to alter nociceptive sensitivity in mice was studied using the tail-flick, hot-plate and formalin tests. Subcutaneous (SC) adminstration of 8-OH-DPAT (0.63–1.0 mg/kg) dose-dependently increased the temperature at which hindpaw lick occurre in a hot-plate test using slowly rising temperature and increased the latencies to hindpaw lick, but reduced the latencies to jump in a conventional hot-plate test. Intracerebroventricular (ICV) injections (0.25–1.0 μg) produced similar results in the conventional hot plate test. Following intrathecal (ITH) injections (0.25–1.0 μg), however, the latencies to hindpaw lick were elevated without any change in jump latencies. In the formalin test a low systemic dose of 8-OH-DPAT (0.63 mg/kg) elicited hyperalgesia, while hypoalgesia was found after a high dose (1.0 mg/kg). ICV injection of 1.0 μg produced hypoalgesia in the formalin test while the same dose injected ITH was without effect. 8-OH-DPAT did not alter tail-flick latencies, either by SC, ICV or ITH administration. Previous studies have shown that 8-OH-DPAT stimulates central serotonergic receptors, and shows selectivity for the 5-HT 1A recognition site. The present findings indicate an involvement of 5-HT 1A receptors in the processing of nociceptive information both at spinal anpraspinal sites. However, stimulation of 5-HT 1A receptors does not seem to affect spinal, nociceptive reflexes.