Figure 4.
Blockade of specific neurotransmitter receptors, synthesis of dilatory mediators, or astroglial metabolism impaired the CBF response evoked by whisker stimulation. A, Neuronal and astroglial pathways and sites of action (indicated by ×) of the different pharmacological tools used. The shaded area indicates that the COX-1 pathway is common to both astrocytes and pyramidal neurons, whereas the P450 epoxygenase and COX-2 pathways are located in astrocytes and neurons, respectively. AA, Arachidonic acid; Indo, indomethacin; PGs, prostaglandins; TCA, tricarboxylic acid. B, Whisker stimulation-evoked CBF responses were reduced after nonselective COX inhibition (indomethacin), an effect mimicked by COX-2 (NS-308), but not COX-1 (SC-560), inhibition. Combined administration of MK-801 and NS-398 did not further inhibit the evoked CBF response. Similarly, combined blockade of COX-2 (NS-398) and NMDA (MK-801) or GABA-A (picrotoxin) receptors did not have a larger effect than NS-398 alone. The evoked CBF response was reduced by inhibition of EET synthesis (MS-PPOH), an effect not potentiated when combined with blockade of NMDA or GABA-A receptors. C, Evoked CBF responses were reduced after antagonism of NMDA receptors with MK-801, of group I mGluRs with MPEP and LY367385, and GABA-A receptors with picrotoxin [either after intracisternal injection or superfusion through a closed cranial window (SPF)]. In contrast, blockade of GABA-B (CGP35348), muscarinic ACh (scopolamine), or VIP [VIP(6–28)] receptors did not alter the evoked CBF response. Combined GABA-A and NMDA receptor blockade with picrotoxin and MK-801 had an additive reducing effect on the evoked CBF when compared with each compound individually. D, Whisker stimulation-evoked CBF increases were reduced after inhibition of astroglial oxidative metabolism (fluorocitrate, fluoroacetate). The number of rats used is indicated within parentheses. Values are mean ± SEM of change versus the evoked CBF response after vehicle injection. *p < 0.05, **p < 0.01, ***p < 0.001 versus vehicle by repeated-measures ANOVA. ★p < 0.05 versus MK-801 or picrotoxin alone, by one-way ANOVA.