Cerebrovascular consequences of altering serotonergic transmission in conscious rat.
Many therapeutic strategies aim at altering serotonin brain levels. However, serotonin (5-HT) is known to influence the cerebral circulation. The purpose of this study was to determine the effects of acutely decreasing intracerebral serotonin release upon cerebral blood flow and cerebrovascular reactivity to hypercapnia in conscious rats. To this end, (1) we analyzed the time-course of cortical blood flow changes measured with laser-Doppler flowmetry following injection of 0.1 mg kg(-1) 8-OHDPAT (5-HT1A agonist), and (2) we evaluated the cerebrovascular reactivity to hypercapnia using a quantitative multiregional diffusible tracer technique 5 and 60 min following 8-OHDPAT administration. 8-OHDPAT induced a rapid and transient increase in cortical blood flow (+34%) that was prevented totally by WAY100135 (5-HT1A antagonist) pre-treatment. Five min following 8-OHDPAT administration, the cerebrovascular responsiveness to hypercapnia was increased significantly in striatum (+27%) and fronto-parietal cortex (+61%). This result is consistent with a vasoconstrictor role of the serotonergic system that becomes manifest during hyperemic conditions.
Bonvento
G
G
Laboratoire de Recherches Cérébrovasculaires, CNRS UA 641, Université Paris 7, France. bonvento@ext.jussieu.fr
Borredon
J
J
Seylaz
J
J
Lacombe
P
P
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D017078:Laser-Doppler Flowmetry; D016014:Linear Models; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D002245:Carbon Dioxide; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin