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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.
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PMID:GABAergic modulation of ethanol-induced motor impairment. 629 99

The characterization and measurement of the benzodiazepine and ethanol interaction has been of major interest for many years. Various pharmacological and biochemical studies have been employed to investigate this interaction, which is believed to occur predominantly in the CNS, but localization of one particular brain area has not been investigated. This research employed the rat cerebellum as a site to study the diazepam/ethanol interaction. The measurement of cerebellar ethanol and diazepam, by gas chromatography, demonstrated an enhancement of diazepam levels by ethanol. Ethanol and diazepam, alone and in combination, displayed a significant depression of cerebellar 3',5'-Guanosine Cyclic Monophosphate (cGMP). The depression seen by the combination was significantly greater than the simple algebraic sum, but insignificantly different from the corrected algebraic sum. The double reciprocal plot of the data demonstrated a common ordinate intercept for the diazepam line and the diazepam/ethanol (2 g/kg) line, thus indicating a competitive mechanism of action.
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PMID:Use of cerebellar cGMP in the measurement and characterization of the diazepam/ethanol interaction. 629 9

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.
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PMID:Alcohol, protein nutrition, and liver injury. 634 74

Ethanol depresses the ventilatory responses to hypercapnia and hypoxia. We hypothesized that this ventilatory depression, like some other central nervous system effects of ethanol, might be mediated via endorphins. In a double-blind placebo-controlled study, we assessed the effect of the opiate antagonist naloxone on ventilatory responses during ethanol intoxication in 18 normal men. Standard rebreathing studies were done at baseline, after ethanol (1.5 ml/kg, p.o.), and after each of 2 intravenously administered injections. One of the injection sequences PP, NP, or PN (N = naloxone, 0.8 mg; P = placebo, 2 ml) was randomly assigned to each subject. The ventilatory responses were reduced after ethanol administration compared with those at baseline (p less than 0.05). In groups NP and PN, naloxone restored the hypercapnic response (p less than 0.05). Placebo injection did not significantly alter the response slopes. Hypoxic ventilatory responses showed the same trends but did not reach statistical significance. This study shows that naloxone reverses ethanol-induced depression of hypercapnic drive, suggesting that an opiate-mediated mechanism is responsible for this depression.
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PMID:Naloxone reverses ethanol-induced depression of hypercapnic drive. 635 14

Ethanol-induced sedation in Sprague-Dawley rats was antagonized by intracisternally administered thyrotropin releasing hormone (TRH) at a dose as low as 1 microgram. Furthermore, when a dose of 25 micrograms or greater of TRH was combined with ethanol doses above 2 g/kg, the locomotor activity was significantly greater than observed for TRH alone. A dose-related increase in activity was observed when varying doses of ethanol were administered with a constant dose of TRH (100 micrograms). This increase in locomotion induced by the TRH-ethanol combination could not be attributed to a change in TRH concentration, ethanol distribution or to a pituitary action of TRH. Inasmuch as tert-butanol in combination with TRH produced the same effects as ethanol, the hyperactivity does not appear to be associated with acetaldehyde formation. TRH acid and His-Pro-diketopiperazine, metabolites of TRH, did not produce hyperactivity when administered with ethanol, whereas MK-771, a TRH analog, produced a significant increase in locomotion in ethanol-treated rats greater than that for MK-771 alone. Three lines of evidence suggested that the hyperactivity induced by the TRH-ethanol combination could not be attributed to an influence of ethanol on the stimulant effects of TRH. First, pentobarbital- and chlordiazepoxide-induced depression of locomotion was antagonized by TRH (100 micrograms) but, unlike ethanol, locomotor stimulation greater than that for TRH was not observed. Second, behavioral observations did not reveal ethanol altering any effects of TRH that would compete with locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ethanol-induced locomotor stimulation in rats after thyrotropin-releasing hormone. 642 48

Complex spike activity was evoked in cerebellar Purkinje cells by submaximal stimulation of the sensory cerebral cortex of urethane anaesthetised rats. Ethanol (1.5 g/kg, i.v. over 10 min) produced a parallel decrease in spontaneous and cerebral cortex-evoked CS activity. The spontaneous firing rate of inferior olive neurones was decreased by ethanol administered intravenously (1.5 g/kg, over 10 min) or locally by micropressure ejection. Thus, the decrease in CS activity produced by ethanol is due to a depression of inferior olive neurones, possibly by a direct action of ethanol on these neurones.
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PMID:Ethanol depresses inferior olive neurones and reduces Purkinje cell complex spike activity evoked by cerebral cortical stimulation. 652 58

The behavioral and neurochemical effects of acute and chronic ethanol administration were studied in BALB/c, C57B1/6 and DBA/2 mice. The rates of dopamine synthesis and release in the striatum were estimated by measuring the accumulation of DOPA and DOPAC, respectively, after inhibition of aromatic amino acid decarboxylase with NSD-1024. Biphasic behavioral effects were found in BALB/c and DBA/2 mice, but not in C57B1/6 mice, with low doses of ethanol producing activation and high doses, depression. Biphasic effects were also found in the dopamine response to acute doses of ethanol. The BALB/c and DBA/2 mice showed larger suppressions of DA release in the lower dose ranges of ethanol, and smaller increases at the higher doses than did the C57B1/6 mice. Ethanol stimulated dopamine synthesis in a monophasic, dose-dependent manner, and C57B1/6 mice were less sensitive to this effect of ethanol compared to the other tested strains of mice. Chronic ethanol feeding produced behavioral tolerance to the high-dose depressant effects of ethanol, but not to the low-dose activating effects. Similarly, tolerance developed in the dopaminergic responses to a higher challenge dose of ethanol (3.5 g/kg). These findings demonstrate that genetically determined differences exist in the sensitivity of the dopaminergic systems of mice to ethanol, and suggest that central dopamine neurons may be important in the behavioral effects of ethanol.
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PMID:Neurochemical correlates of tolerance and strain differences in the neurochemical effects of ethanol. 668 1

The effects of ethanol and acetaldehyde on basal tension of canine small and large coronary arteries were examined in vitro. Ethanol in a concentration as little as 8.5 mM can induce threshold contractions of coronary arteries. High concentrations of ethanol produce concentration-dependent coronary vasospasms equivalent to those induced by supra-maximal concentrations of KCl. Acetaldehyde (10(-5) to 10(-2)M) resulted in concentration-dependent relaxation of basal tone. Use of a variety of pharmacological antagonists (i.e., phentolamine, methysergide, diphenhydramine, metiamide, propranolol and indomethacin) did not attenuate or prevent the spasmogenic actions of ethanol. These findings could help to explain why alcohol can induce cardiac depression, arrhythmias, cardiomyopathy and the higher than normal incidence of sudden death observed in 'binge' drinkers.
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PMID:Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle. 683 Nov 12

Two new lines of rats have been selectively bred for high or low active avoidance responding--the Australian High (AHA) and Low (ALA) Avoiders. Ethanol (1-1.5 g/kg body weight, i.p.) improved acquisition of active avoidance responding only in ALA, whereas alpha-methyl-p-tyrosine (AMPT; 80 mg/kg body weight, i.p.) seemed to selectively impair acquisition of responding in AHA. The combination of ethanol and AMPT caused a general depression of behaviour. The 2 lines did not differ consistently in the latency to escape from shock, locomotor activity, 'emotionality' or passive avoidance responding. Ethanol had no effect on locomotor activity or 'emotionality', but increased the latency to escape from shock and impaired passive avoidance responding in both lines.
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PMID:The Australian High and Low avoidance rat strains: differential effects of ethanol and alpha-methyl-p-tyrosine. 687 Oct 17

The specific effect of ethanol on several aspects of the gel-to-liquid crystal transition of dipalmitoylphosphatidylcholine was investigated using two spectrophotometric techniques, one probe method and one direct method. Ethanol shifts the phase-transition temperature to low temperature, demonstrating that ethanol interacts preferentially with the fluid phase. Thermodynamic analysis of the melting point depression leads to a calculated membrane:buffer partition coefficient of 6.25 (mole fraction units) or 0.15 mole of ethanol per kilogram of lipid:mole of ethanol per liter of solution. Careful evaluation of the transition cooperativity with temperature resolution of +/- 0.1 degrees shows that there is no reduction in transition cooperativity, and thus no reduction in size of the cooperative lipid clusters due to ethanol. The implications of these findings for the mechanism of action of ethanol in terms of current theories of anesthetic mechanisms are discussed.
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PMID:The effects of ethanol on the thermotropic properties of dipalmitoylphosphatidylcholine. 689 3


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