Effects of the putative 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)tetralin on nociceptive sensitivity in mice.

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) administration of 8-OH-DPAT (0.63-1.0 mg/kg) dose-dependently increased the temperature at which hindpaw lick occurred 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 microgram) produced similar results in the conventional hot plate test. Following intrathecal (ITH) injections (0.25-1.0 microgram), 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 (0.063 mg/kg) elicited hyperalgesia, while hypoalgesia was found after a high dose (1.0 mg/kg). ICV injection of 1.0 microgram 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-HT1A recognition site. The present findings indicate an involvement of 5-HT1A receptors in the processing of nociceptive information both at spinal and supraspinal sites. However, stimulation of 5-HT1A receptors does not seem to affect spinal, nociceptive reflexes.