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SAMMARY AND CONCLUSIONThe mechanisms of action of general anaesthesia are not completely understood. Enhancement of inhibitory postsynaptic responses and inhibition of excitatory synaptic transmission are generally thought to be the predominant mode of general anaesthetics action in the centeral nervous system.Adequate surgical anaesthesia must achieve three goals: immobility, amnesia and absence of awareness. Anaesthetics act on different regions of the nervous system to produce immobilization, amnesia and absence of awarness. Immbolization is very likely mediated by cortex probabily mediate amnesia. A comprehensive explanation of the mechanism by which anaesthetics cause loss of consciousness has not been yet developed. Abundant In vitro and In vivo evidence has been provided of effects of anaesthetics on a wide variety of molecular and cellular processes.The inhibitory GABAA receptor has been considered a potential target site for anaesthetics. Because clinically relevent concentrations of inhalational anaesthetics potentiate its response, inhibition of neuronal nAcHRs by anaesthetics was also found.The aim of the present study is to clarify the effects of some intravenous anaesthetics like midazolam, propofol, thiopental and some inhalational anaesthtic as halothane and isoflurane on the level of neurotransmitters GABA and acetycholine in rat brain.Procedure for determination of GABA content in whole and regional areas in the rat brain:Seventy two male albino rats (150-180g) were used in this study and were divided into equal 6 groups, each containing 12 rats.Control group (I) receiving saline intraperitoneal, group (II) receiving halothane at 1 MAC, group (III) receiving isoflurane 1 MAC, group (IV) receiving sodium thiopental as an intraperitoneal dose of 20-40 mg/kg, group (V) receiving midazolam as an intraperitoneal dose of 2.5-10 mg/kg and group (VI) receiving propofol as an intraperitoneal dose of 50 mg/kg. The end point in groups II, III, IV, V and VI was absence of movement to tail-clamp. The rats were decapitated and the brains were quickly removed and placed on ice-cold Petri-dishes. The 12 animals in each group were subdivided into 2 subgroups; each containing 6 rats for preparation of whole brain and the other 6 rat brains were dissected into cerebral cortex, thalamus, mid-brain and hind- brain areas. The specimens were weighed and frozen on dry ice, stored at -80?C in liquid nitrogen until assayed.Tissues were placed in 10-ml plastic tubes (Falcon Tubes) containing 1000 ?g valine solution per gram of sample and 15 volumes of 75?C ethanol HPLC grade. Then samples were homogenized centrifuged by cooling centrifuge and dervitized by processed with dansyl chloride and injected directly into HPLC system. The results expressed as area%.Procedure for determination of Ach content in whole and regional areas in the rat brain:The same procedure used in GABA determination were used for determination of acetylcholine with some modification used specifically for acetylcholine. Samples containing 0.15 mM PEP were processed and injected into HPLC system. Also results were expressed as area%.Results:There was a significant increase of GABA level in whole brain with intravenous anaesthetics by 259.8%, 228.1% and 13.3% under the effect of propofol, thiopental and midazolam respectively. Also inhalational anaesthetics show slight increase in GABA level by 23.4% and 14.4% under the effect of isoflurane and halothane in comparison to control.Similarly, there were increase in GABA level in cortex, thalamus, mid brain and hind-brain with highly to slightly differences between different areas.There was a significant decrease of Ach level in whole brain with intravenous anaesthetics by 72.2%, 64.8% and 35.5% under the effect of propofol, thiopental and midazolam respectively. Also inhalational anaesthetics show decrease in Ach level by 54.3% and 60.2% under the effect of isoflurane and halothane in comparison to control.Similarly, there were highly to slightly significant decrease in Ach level in cortex, thalamus, mid brain and hind-brain.Conclusion:Intravenous and inhalational anaesthetics increase GABA level and decrease Ach level in whole brain and different brain areas. For agiven anaesthetics multiple sites of action contribute in an additive manner to produce an overall pressure of transmission through the neuronal circuit. For each anaesthetic the degree of effect is agent specific at some of these sites. Together, this supports a multi-site agent specific mechanism of action of general anaesthetics.Future advances in anaesthetic mechanisms will go hand in hand with more recent studies with (FMRI) and (PET) to map changes in regional (CBF) associated with anaesthetic effects. Also, genetic studies can be viewed as promising complement to pharmacological, biochemical and physiological studies.Recommendations:? The design of safer and more effective therapeutic agents for anaesthesia; that exihabit fewer undesirable side effects; should be from agents which selectively target GABA and glutamate.? Patients could be at risk of intraoperative awakening if reversal of neuromuscular block using physostigmine occurs during anaesthesia.REFERENCESAburawi S, Abdullah S. Elhuwuegi, Saleems. Suher M. Ahmed, Samir F Saad and Amira S (2000): Effects of acute and chronic triazolam treatments on brain GABA levels in albino rats. Acta Neurobiol. Exp.; 60: 447-455.Akaike N, Maruyama T, Tokutomi N (1987): Kinetic properties of the pentobarbitone-gated chloride current in frog sensory neurons. J physiol; 394:85-98.Alberstone CD, Skirboll SL, Benzel EC, (2000): Magnetic source imaging and brain surgery: presurgical and intraoperative planning in 26 patients. J Neurosurg; 92: 79-90.Albertson TE, Walby WF, Joy RM (1992): modification of GABA mediated inhibition by various injectable anesthetices. Anesthesiology 77; 488-99.Alkire MT and Haier RJ (2001): Correlating in vivo anaesthetic effects with ex-vivo receptor density supports a G
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