5-HT1A agonists have been recently demonstrated to restore normal breathing rhythm in cats made apneustic by systemic MK-801 administration (Lalley et al., 1994) as well as in a case report of a child with a apneustic pattern of breathing (Wilken et al., 1997). Preliminary data from our laboratory suggest the 5-HT1A agonist 8-OH-DPAT may be capable of effecting recovery from multiple respiratory disorders caused by disturbances in several neurotransmitter system involved in respiratory circuits. Rescue from some of these disorders have been reported while others have not been addressed in the literature.
The aims of this proposal are: 1) To determine 5-HT1A agonist potential for reversing respiratory alterations produced by competitive NMDA receptor antagonists, morphine, baclofen, lidocaine and tetrodotoxin. 2) To examine the specificity of the response to 5-HT1A agonists and address the question of whether post-synaptic and somatodendritic 5-HT1A receptors are involved. 3) To determine whether 5-HT1A antagonists will exacerbate the deleterious effects of NMDA antagonists as well as those produced by intravenous and microinjected baclofen, and 4) To locate the site or sites of action in the brain where 5-HT1A agonists produce rescue from respiratory depression.
