Acetylcholine Release In Cerebral Cortex Research Articles

Effects of dexmedetomidine, midazolam, and propofol on acetylcholine release in the rat cerebral cortex in vivo

Acetylcholine plays an important role as a neurotransmitter in the central nervous system with involvement in both sleep and arousal. Dexmedetomidine, midazolam, and propofol are widely used for sedation of patients in intensive care medicine. In this study, we have examined the effect of continuous administration of dexmedetomidine, midazolam, and propofol on acetylcholine release in the rat cerebral cortex, using an in vivo microdialysis technique. Following infusion of a control solution, male Wistar rats (n = 6/group) were administered dexmedetomidine at 0.3 μg/kg/min, midazolam at 20 mg/kg/h, or propofol at 50 mg/kg/h over a 2-h period. Using a brain microdialysis method, extracellular acetylcholine concentrations were measured up to 2 h after administration of each agent at 15-min intervals. In the midazolam group, acetylcholine levels were significantly reduced with midazolam infusion, remaining low even after the drug was stopped. In the propofol group, acetylcholine levels were significantly decreased during propofol infusion, but returned to control levels once the infusion was stopped. Dexmedetomidine administration decreased acetylcholine release, but this finding was not statistically significant. From this study, midazolam and propofol but not dexmedetomidine significantly suppressed acetylcholine release in the cerebral cortex at sedative doses. Even though the righting reflex recovered almost the same after the cessation of drug administration, midazolam suppressed acetylcholine release longer than propofol.

Cutaneous mechanical sensory stimulation increases extracellular acetylcholine release in cerebral cortex in anesthetized rats

The effects of noxious and innocuous mechanical stimulation of various segmental skin areas (face, forelimb and paw, back, hindlimb and paw) on extracellular acetylcholine release in the cerebral cortex in the parietal lobe were examined in halothane-anesthetized rats, by means of the microdialysis technique. Pinching of a forepaw or hindpaw and brushing of a hindlimb for 10 min produced significant increases in extracellular acetylcholine release, whereas pinching of the face or back and brushing of the face, forelimb or back produced no significant changes. These results demonstrate that cutaneous sensory stimulation can regulate extracellular acetylcholine release in the cerebral cortex, and that the efficacy of the stimulation on cortical acetylcholine release is dependent on the sensory modality and the region of skin stimulated.

Effect of lesion of the nucleus basalis of rat on acetylcholine release in cerebral cortex: time course of compensatory events

Excitotoxin lesion of the nucleus basalis of the rat causes a substantial reduction in the K +-evoked release of [ 3H]acetylcholine (ACh) from tissue slices of ipsilateral frontal and parietal cortex. Decreases in the K +-evoked release of [ 3H]ACh (nCi/mg protein) of 71% and 47% are seen 21 days after lesion in the frontal and parietal cortex respectively. However, in later periods a considerable reversal of this deficit occurred which was complete in parietal cortex at 102 days, when the K +-evoked release of [ 3H]ACh was not significantly different from the controls. In the frontal cortex where a greater decrease in acetylcholinesterase (AChE) is obtained, a similar but attenuated reversal occurred, the K +-evoked release of [ 3H]ACh reaching 75% of the control value at 128 days after lesion. The compensatory changes in [ 3H]ACh release were paralleled by changes in AChE in both regions. Despite the reduced level of release following lesion, the K +-evoked release of [ 3H]ACh was responsive to the inhibitory effect of the cholinergic agonist, oxotremorine. Lesions outside the nucleus basalis produced no changes in the release of [ 3H]ACh from frontal or parietal cortex. All lesions were verified histologically. The compensatory changes reported are discussed in terms of the growth of ‘sprouts’ from the spared cholinergic axons. This study clearly demonstrates that compensatory changes in complex systems such as transmitter release which markedly affect cholinergic function do occur in response to lesion in common with other presynaptic parameters.

GABA induced changes in acetylcholine release from slices of guinea-pig brain.

The effect of GABA on acetylcholine (ACh) release was investigated on superfused slices of guinea-pig cerebral cortex (CC), caudate nucleus (CN), tuberculum olfactorium and brain stem. GABA (1--6 x 10(-3) mol/l) increased the spontaneous and KCl-evoked ACh overflow in CC and CN, reduced the electrically-evoked release in all areas tested (most evidently in CC and CN) and lowered the threshold of electric stimulation-induced ACh release in CC. These effects were also caused by 3-amino-1-propane sulphonic acid (1 x 10(-3) mol/l) and ethanolamine-O-sulphate (2 x 10(-3) mol/l), were reduced by bicuculline (1 x 10(-4) mol/l) and fully antagonized by picrotoxin (8 x 10(-5) mol/l), but they were not influenced by phentolamine, methysergide, spiroperidol or strychnine. Tetrodotoxin (TTX) (5 x 10(-7) mol/l) blocked the facilitation of spontaneous ACh release by GABA only when the slices were perfused with normal Krebs solution, but not when perfused with a KCl-enriched medium. These results suggest that GABA affects the cholinergic transmitter release through bicuculline- and picrotoxin-sensitive receptors, showing low affinity toward the agonist. Moreover GABA modulation of resting ACh release requires action potentials only in normal [K+]0, but not in high [K+]0, suggesting that GABA-receptive sites are located at cholinergic terminals.