PROTECTIVE EFFECTS OF 5-HT1A RECEPTOR AGONISTS AGAINST NEURONAL DAMAGE DEMONSTRATED IN-VIVO AND IN-VITRO

The aim of the present study was to evaluate the neuroprotective effec t of the 5-hydroxytryptamine(1A) (5-HT1A) agonists, CM 57493 and urapi dil, in vivo and in vitro, respectively In vivo permanent occlusion of the middle cerebral artery (MCA) was performed in male Wistar rats. F orty-eight hours after electrocoagulation of the MCA the infarct volum e was determined. Pretreatment of the rat with the 5-HT1A agonist urap idil significantly reduced infarct development. The neuroprotective ef fect of the agent was restricted to the cortical area; the striatal da mage was not influenced. As the stimulation of the 5-HT1A receptor by serotonin is supposed to induce inhibitory, hyperpolarizing effects by opening of a Ca2+-independent neuronal K+ ionophore, the efficacy of agonistic drugs directly on the neuron was investigated in vitro. Cyan ide-induced cytotoxic hypoxia as well as glutamate-induced excitotoxic ity were performed using primary neuronal cell cultures from chick emb ryo cerebral hemispheres. Treatment with the 5-HT1A agonists urapidil and CM 57493 significantly increased protein content of hypoxic cultur es. CM 57493 added to the culture medium (1-10 mu M) during and up to 24 h after glutamate exposure ameliorated viability of the neurons. Th e results demonstrate neuroprotective potency of the 5-HT1A agonists, urapidil and CM 57493, when applied under hypoxic, excitotoxic and isc hemic conditions in vivo and in vitro, respectively. Both, presynaptic ally induced inhibition of glutamate release as well as postsynaptical ly induced inhibition of neuronal excitability could be discussed as p ossible mechanisms of action of the 5-HT1A receptor agonism.