TY - JOUR T1 - Reversal of Morphine-Induced Apnea in the Anesthetized Rat by Drugs that Activate 5-Hydroxytryptamine<sub>1A</sub>Receptors JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 704 LP - 713 VL - 292 IS - 2 AU - Niaz Sahibzada AU - Manuel Ferreira AU - Adam M. Wasserman AU - Angelo M. Taveira-DaSilva AU - Richard A. Gillis Y1 - 2000/02/01 UR - http://jpet.aspetjournals.org/content/292/2/704.abstract N2 - The purpose of our study was to test the hypothesis that 5-hydroxytryptamine (5-HT)1A receptor agonists counteract morphine-induced respiratory depression. Studies were conducted in anesthetized rats, and respiratory activity was monitored with diaphragm electromyography. Morphine was administered i.v. in doses that produce apnea. Once apnea was established, i.v. administration of the 5-HT1A receptor agonist drug 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) at 10 or 100 μg/kg restored normal breathing in each animal (n = 24). This antagonistic effect of 8-OH-DPAT on morphine-induced respiratory depression was observed in both spontaneously breathing and artificially ventilated animals. Results obtained with 8-OH-DPAT were mimicked by buspirone (50 μg/kg i.v.), another 5-HT1A receptor agonist drug. Pretreatment with 4-(2′-methoxyphenyl)-1-[2′[N-(2′-pyridinyl]-p-iodo-benzamido]ethyl]piperazine, an antagonist of 5-HT1A receptors, prevented 8-OH-DPAT from counteracting morphine-induced apnea. These results indicate that activation of central nervous system 5-HT1A receptors is an effective way of reversing morphine-induced respiratory depression. Most important, this is the third model of disturbed respiratory function in which drugs that stimulate 5-HT1A receptors have been shown to restore breathing to near-normal levels. The American Society for Pharmacology and Experimental Therapeutics ER -