Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the sleep profile of the Flinders Sensitive Line (FSL) of rats, which were selectively bred for supersensitive responsivity to an acetylcholinesterase inhibitor (DFP). These animals have an increased density of muscarinic receptors in striatum and hippocampus and display a number of behavioral and neuroendocrine characteristics that may represent a rodent analogue of clinical depression. A continuous 48-hour sleep EEG recording was obtained. Compared to control rats (the Flinders Resistant Line), the FSL rats had selectively more rapid-eye-movement (REM) sleep as a percentage of total sleep time. In addition, the REM sleep latency was significantly shorter and the REM-REM cycle length was significantly faster in the FSL than in the FRL strain. The two strains did not differ in total sleep time, drowsy sleep, or slow-wave sleep. The increased REM sleep in the FSL rats is consistent with the amassed evidence that cholinergic mechanisms selectively promote REM sleep, and suggests that the FSL rats may be useful in understanding the mechanism responsible for short REM latency in depression and narcolepsy.
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PMID:Increased REM sleep in rats selectively bred for cholinergic hyperactivity. 325 94

Response of cholinesterase to dermal exposure of acute, single and multiple doses of Bromophos in the female rat has been studied. Dose-response studies (50-4000 mg/kg body weight, 24 h exposure) showed that plasma cholinesterase was most sensitive to inhibition in vivo, followed by the brain and erythrocyte acetylcholinesterase. The ID50 values for the in vivo cholinesterase inhibition were 10.1, 576.1 and 1938.0 mg/kg body weight for the plasma, brain and erythrocytes, respectively. In time-course studies after a single sublethal dose of 1000 mg/kg body weight (24 h) of Bromophos, the serum and brain cholinesterase were rapidly inhibited reaching a maximum at 16 h. Recovery was complete in the case of serum at 14 days post-exposure, whereas the brain enzyme was not fully recovered at 21 days. In a subacute study, daily dermal application of 50 mg/kg body weight of Bromophos for 5 and 10 days, resulted in high inhibition of the serum cholinesterase and brain acetylcholinesterase, the former being more marked which was reversible after 10 or 15 days of post-exposure period. Very low levels of dermal exposure of Bromophos (10-50 mg/kg body weight) for 17 days caused pronounced depression of serum cholinesterase which completely recovered in 15 days after cessation of exposure suggesting that the serum cholinesterase could serve as the most sensitive diagnostic indicator of Bromophos exposure.
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PMID:Response of blood and brain cholinesterase to dermal exposure of bromophos in the rat. 334 Oct 46

The in vivo time course of cholinesterase inhibition was measured in brain, lung, spleen, hind limb skeletal muscle, diaphragm, intestine, kidney, heart, liver, and plasma of rats receiving 90 micrograms/kg soman, im. This dose of soman produced severe respiratory depression and transient hypertension, but no significant changes in the cardiac output or heart rate of anesthetized rats. The rate and maximal extent of in vivo cholinesterase inhibition by soman varied widely among the tissues. Although cardiac output was unchanged by soman administration, the blood flow in heart, brain, and lung (bronchial arterial flow and arteriovenous shunts) was increased, whereas blood flow in spleen, kidney, and skeletal muscle was decreased. The relative importance of tissue blood flow, tissue levels of cholinesterase and acetylcholinesterase, and tissue levels of soman-detoxifying enzymes (diisopropyl-fluorophosphatase and carboxylesterase) in determining the in vivo rate and maximal extent of cholinesterase inhibition was examined by multiple regression analysis. The best multiple regression model for the maximal extent of cholinesterase inhibition could explain only 63% of the observed variation. The best multiple regression model for the in vivo rate of cholinesterase inhibition contained three independent variables (blood flow, carboxylesterase, and cholinesterase) and could account for 94% of the observed variation. Of these three variables blood flow was the most important, accounting for 79% of the variation in the in vivo rate of cholinesterase inhibition. This suggests that it may be possible to use a flow-limited physiological pharmacokinetic model to describe the kinetics of in vivo cholinesterase inhibition by soman.
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PMID:The effects of blood flow and detoxification on in vivo cholinesterase inhibition by soman in rats. 356 32

The effects of status epilepticus on the concentration, synthesis, release, and subcellular localization of acetylcholine, the concentration of choline, and the activity of acetylcholinesterase in rat brain regions were studied. Generalized convulsive status epilepticus was induced by the administration of pilocarpine to lithium-treated rats. The concentration of acetylcholine in the cortex, hippocampus, and striatum decreased prior to the onset of spike activity or status epilepticus. Once status epilepticus began, the concentration of acetylcholine increased over time in the cortex and hippocampus, reaching peak levels that were 461% and 304% of control levels, respectively, after 2 h of seizures. Such high in vivo levels of acetylcholine had not been reported previously following any treatment. During status epilepticus, the concentration of acetylcholine in the striatum returned to control levels after the initial depression, but did not accumulate to high levels as it did in the other two regions. The in vivo cortical efflux of acetylcholine was also increased during the seizures. Choline levels were increased by status epilepticus in all three brain regions. Inhibition of seizures by pretreatment with atropine blocked the increases of acetylcholine and choline. Synaptosomes prepared from the cortex and from the hippocampus of rats with status epilepticus had elevated concentrations of acetylcholine: in the hippocampus the acetylcholine was principally in the cytoplasmic fraction, whereas in the cortex the acetylcholine was elevated in both the cytoplasmic and the vesicular fractions. The extra acetylcholine was in a releasable compartment, since increased K+ in the media or ouabain increased the release of acetylcholine from cortical slices to a greater extent in tissue from seized rats than from controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine content in rat brain is elevated by status epilepticus induced by lithium and pilocarpine. 361 32

We have studied the effects of anaesthesia on the changes in central respiratory activity following the inhibition of acetylcholinesterase in chronically implanted cats. The organophosphate paraoxon was administered to the brainstem respiratory centres by intracerebroventricular (i.c.v.) injection (3 mg) into the IVth ventricle, thus avoiding peripheral effects such as paralysis of respiratory muscles. Paraoxon had opposite effects on respiratory activity depending on whether the cats were anaesthetized or not: it induced respiratory depression and sometimes respiratory arrest during pentobarbital (30 mg/kg i.v.) or halothane anaesthesia, but in the same animals in the waking state, the same dose of paraoxon always stimulated respiration. These results show a strong interaction between anaesthetics and the effects of acetylcholine (ACh) accumulation on central respiratory activity. This study extends previous results showing an interaction between ACh and pentobarbital on single respiratory neurons and stresses the importance of a 'wakefulness stimulus' for sustaining respiratory activity after organophosphate poisoning.
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PMID:Central respiratory depression induced by acetylcholinesterase inhibition: involvement of anaesthesia. 369 38

The chronic effects of sublethal injections of the cholinesterase inhibitor, paraoxon, on transmitter release were examined in the rat. Rats were chronically treated daily with the organophosphate, paraoxon (0.3 mg/kg b.wt.), that is known to inhibit acetylcholinesterase irreversibly. Severe symptoms of intoxication were evident in animals during the first few days of treatment but by day 11 the symptoms disappeared despite continued treatment and depression in acetylcholinesterase. Intracellular recording techniques were used to determine if the observed behavioral changes to chronic treatment could be correlated with changes in neuromuscular transmission. Measurements of MEPPs demonstrated that tolerance could not be attributed to a decrease in postsynaptic sensitivity. Measurements of EPPs, quantal release and binomial statistical parameters demonstrated that tolerance can be correlated with presynaptic changes. Chronic treatment with paraoxon decreased transmitter release and this can be attributed to a decrease in the transmitter store and mobilization ability. It is suggested that the depression in quantal release at the neuromuscular junction and at cholinergic synapses could account for behavioral tolerance.
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PMID:Chronic effects of paraoxon on transmitter release and the synaptic contribution to tolerance. 371 75

Neuropathological and biochemical effects of neonatal exposure to the alkyl metal triethyltin were examined in juvenile male Long Evans rats. Rats were injected intraperitoneally on postnatal day 5 with 6 mg/kg of triethyltin bromide and sampled on day 20. The brains of tin-treated animals weighed significantly less than either saline or starved controls and exhibited a marked caviation of the ventrolateral surfaces. Histologically, neuronal necrosis was noted in the entorhinal and transitional cortex, an observation confirmed by immunocytochemical staining of astrocytes. Hippocampal involvement was further evidenced by a protrusion of the molecular layer of the dentate gyrus, and an abnormal histochemical staining pattern of acetylcholinesterase in this layer. Sections stained by the Timm's method for the deposition of heavy metals showed a marked reduction in the staining of the hippocampal CA4,3,2 sectors and an absence of stained laminae in the outer molecular layer of the dentate gyrus. Receptor binding assays indicated a selective depression of the benzodiazepine receptor in the hippocampus of tin-treated pups compared to starved controls. Taken in concert, these data indicate that neonatal exposure to triethyltin produces severe neuronal damage in the posterior cortex and a derangement of hippocampal afferent circuitry.
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PMID:Triethyltin-induced neuronal damage in neonatally exposed rats. 371 27

The response of the atrioventricular (AV) junction to brief intense adrenergic stimulation applied during episodes of second degree heart block achieved by acetylcholinesterase paralysis in the AV junction was examined in six dogs. Despite profound depression of AV conduction due to enhanced cholinergic activity, strong local adrenergic stimulation still readily elicited AV junctional tachycardia. Increase in cholinomimetic influences in the AV junction did not prolong transatrial or His bundle-ventricular conduction times. During AV junctional rhythm and retrograde atrial capture (n = 4), neither the sequence of retrograde atrial activation nor the atrial electrogram configurations were altered. In the two remaining dogs the AV junctional tachycardia was associated with AV dissociation. These findings suggest that the acetylcholine-induced depression of AV conduction is located in the AV node region exclusively. More important, however, is the demonstration that retrograde atrial activation originating from a pacemaker located in the AV node or immediate vicinity could actually precede the inscription of the H spike by a considerable amount of time, further suggesting that anterograde conduction from the pacemaker site to the bundle of His is far more depressed by acetylcholine than is the concomitant retrograde conduction from the pacemaker site to the atrium. Thus, inference of the origin of a subsidiary pacemaker from the P wave configuration or the relation of the A wave to the His bundle electrogram, or both, may lead to erroneous conclusions.
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PMID:Atrioventricular junctional tachycardia during heart block. 374 13

The changes in brain acetylcholinesterase (AChE), acid phosphatase (APase), and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP), and plasma butyrylcholinesterase (BuChE) activities were investigated in hens treated with a single, dermal dose (100-1000 mg/kg) of S,S,S-tri-n-butyl phosphorotrithioate (DEF). Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control). Brain AChE activity, determined 28 days after application, was significantly inhibited in hens given 500-1,000 mg/kg DEF and in TOCP- and parathion-treated hens. In contrast, brain APase and CNP activities were significantly higher in all treatments as compared with those of the untreated hens. Parathion, however, caused the least increase in these enzymatic activities as compared to DEF or TOCP. A single, dermal dose of DEF or TOCP also caused an initial decrease in plasma BuChE activity with maximum depression of enzymatic activity observed 1 to 7 days after administration. This decrease was dose dependent and the enzymatic activity showed partial recovery with time. Hens treated with single, dermal doses of DEF, ranging from 250 to 1000 mg/kg, developed ataxia which progressed to paralysis in some hens. Histopathologic examination revealed axon and myelin degeneration of the spinal cord and peripheral nerves of some hens. The severity and frequency of the neuropathologic lesions were dose dependent. Neurologic dysfunctions and neuropathologic lesions seen in DEF-treated hens were similar to those exhibited in TOCP-treated hens. While parathion produced acute cholinergic effects, it did not cause delayed neurotoxicity. The changes in brain and plasma enzymes are discussed in relation to their role in the pathogenesis of DEF-induced delayed neurotoxicity.
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PMID:Brain acetylcholinesterase, acid phosphatase, and 2',3'-cyclic nucleotide-3'-phosphohydrolase and plasma butyrylcholinesterase activities in hens treated with a single dermal neurotoxic dose of S,S,S-tri-n-butyl phosphorotrithioate. 395 29

The acute effects of diisopropylfluorophosphate (DFP) were assessed in DBA/2Ibg, C57BL/6Ibg and C3H/2Ibg mice. The DFP was administered by intraperitoneal injection in saline. Brain acetylcholinesterase (AChE) activity was maximally inhibited within 5 min after injection. All mice showed signs of organophosphate intoxication including salivation, lacrimation, diarrhea, respiratory distress, tremor and, at high doses, seizures. The C57BL mice were most susceptible to these effects of DFP. The LD50 values for DFP were 8.0, 7.6, and 6.8 mg/kg for male DBA, C3H, and C57BL mice, respectively. The LD50 values for females were nearly the same. Body temperature and brain AChE activity decreased in a dose-dependent manner following injections of DFP of 3.17, 4.22, 5.28, and 6.33 mg/kg. Maximum temperature depression occurred 2 hours after DFP administration; by 24 hours temperatures had returned to normal except for C57BL mice treated with the highest dose of DFP. The C57BL strain was most susceptible to the DFP-induced hypothermia, the C3H strain was the most resistant, and the DBA strain was intermediate. Maximum temperature depression and residual AChE activity, as measured 24 hours after injection, were linearly related. These strain differences do not seem to be explained easily by a differential inhibition of AChE activity.
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PMID:Genetically determined differences in acute responses to diisopropylfluorophosphate. 399 71


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