Data from a number of studies provide evidence that H-HT1A receptors play a seminal role in the maintenance of normal respiratory drive. Activation of 5-HT1A has been shown to enhance respiratory function in normal breathing animals, and restore respiratory function to normal in animals that exhibit life threatening impairment in breathing. Recently, our own studies provide evidence that this phenomenon of restoration of respiratory rhythm extends to a number of models of respiratory disturbance. Thus, intravenous administration of 5-HT1A agonists, in particular 8-OH-DPAT and buspirone, will restore breathing to normal rats that: (1) exhibit morphine-induced apnea; (2) experience apneusis or apnea from excessive doses of an antagonist of the NMDA receptor complex, namely from an overdose of dizocilpine; and (3) pentobarbital- induced apnea. Finally, we have reported that 8-IOH-DPAT and buspirone will restore normal breathing to rats that have disturbed respiratory function caused by spinal cord injury. These findings suggest that we may have discovered a new pharmacological approach to treating disturbances in respiratory function. This is a field of drug therapy that has been woefully neglected largely because most drugs developed for this purpose in the past have convulsant properties. Equally important, these findings indicate that the serotonergic system may be having a major influence on the control of respiration. Studies are proposed to investigate: (1) if activation of 5-HT1A receptors will improve respiratory function in animals with impaired breathing under any experimental condition (e.g., barbiturate overdose, a mixture of drugs that depress breathing, etc.); (2) whether 5-HT1A receptor agonists exert their beneficial effect on breathing because they enhance or depress the activity of the serotonergic system; (3) the site(s) of respiratory neurons that are affected by 5-HT1A receptor antagonists. The results of the proposed research will provide insights into novel therapeutic applications for respiratory disturbances following drug overdose or spinal cord injury.
| Dorsey, Charles H; Cousin, Carolyn E; Lewis, Fred A et al. (2002) Ultrastructure of the Schistosoma mansoni cercaria. Micron 33:279-323 |
