Ethanol Withdrawal Symptoms and Ethanol-induced Neuropathology Effects of Dexmedetomidine Treatment and Aging

............................................................................................................................................................... 8 Review of the literature....................................................................................................................................... 9 1 Ethanol and the nervous system ................................................................................................................. 9 1.1 Morphological and functional alterations of the human nervous system after chronic ethanol exposure ............................................................................................................................................... 9 1.2 Pathophysiological mechanisms behind ethanol-induced neuronal degeneration .......................... 11 1.2.1 A review of general mechanisms............................................................................................... 11 1.2.2 Neurotransmitters in ethanol-induced neuronal degeneration .................................................. 12 1.3 Neurotransmitters in chronic ethanol exposure, ethanol preference and dependence .................... 14 1.4 The ethanol withdrawal syndrome .................................................................................................... 15 1.5 The adrenergic neuron as a model of ethanol-induced neuronal degeneration ............................... 20 1.6 Interactions of ethanol and aging on the nervous system................................................................. 22 1.7 Effects of aging on ethanol withdrawal symptoms .......................................................................... 23 2 Treatment of the ethanol withdrawal syndrome ...................................................................................... 24 3 Dexmedetomidine, a potent and selective alpha-2-adrenergic agonist................................................... 27 The aims of the study ........................................................................................................................................ 30 Materials and methods ...................................................................................................................................... 32 1 Experimental animals ............................................................................................................................... 32 2 Ethical considerations ............................................................................................................................... 32 3 Ethanol exposures and medications ......................................................................................................... 32 3.1 Ethanol feedings (I, II, III, IV, V) ..................................................................................................... 32 3.2 The four-day ethanol exposure (I, II)................................................................................................ 33 3.3 The 12-day ethanol exposure (III)..................................................................................................... 34 3.4 The 5-week intermittent ethanol exposure (IV, V)........................................................................... 34 4 Measurement of the ethanol withdrawal symptoms (I, II, IV, V)........................................................... 36 5 Blood ethanol concentrations (III, IV, V) ................................................................................................ 37 6 Tissue preparation and histological methods (III, IV, V)........................................................................ 38 6.1 Histological procedures of the superior cervical ganglion (III) ....................................................... 38 6.2 Histological procedures of the locus coeruleus (IV, V) ................................................................... 39 7 Morphometric analyses (III, IV, V).......................................................................................................... 40 7.1 Morphometric analyses of the superior cervical ganglion (III) ....................................................... 40 7.2 Morphometric analyses of the locus coeruleus (IV, V).................................................................... 40 8 Statistical methods .................................................................................................................................... 41 Results................................................................................................................................................................ 43 1 Blood ethanol concentrations and ethanol tolerence (III, IV, V)............................................................ 43 2 Dexmedetomidine in the treatment of ethanol withdrawal symptoms (I, II, IV, V) .............................. 44 3 Morphology of the adrenergic neurons and neuroprotective effects of dexmedetomidine (III, IV) ..... 46 4 Effects of aging on ethanol withdrawal symptoms and ethanol-induced neuronal degeneration (V)... 48