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L G Costa

Publications and source records attributed to L G Costa.

At least 127 records · Page 7Linked to original sources
PubMed1990

Interaction of sigma-compounds with receptor-stimulated phosphoinositide metabolism in the rat brain.

Sigma-receptors are nonopioid, nondopaminergic receptors that bind with high affinity several antipsychotic drugs and appear to be involved in regulation of posture and movement. The second messenger system coupled to these receptors is still unknown. Recently, an inhibitory effect of various sigma-compounds on carbachol-stimulated phosphoinositide metabolism has been reported. We have investigated the effect of six sigma-compounds on carbachol- and norepinephrine-stimulated 3H-inositol phosphate accumulation in rat cerebral cortex slices. All compounds tested had a dose-dependent inhibitory effect on both systems, although their order of potency differed between neurotransmitters. Pentazocine and 1,3-di-o-tolylguanidine were the most potent inhibitors of carbachol-stimulated phosphoinositide turnover (IC50 = 31.5 and 45.7 microM, respectively), while haloperidol showed the greatest potency on the norepinephrine-coupled system (IC50 = 3.5 microM). In the presence of IC50 concentrations of these inhibitors, the dose-response curves for the agonists were shifted to the right and the EC50 values were significantly increased. Sigma-compounds also inhibited the binding of [3H]quinuclidinyl benzilate to muscarinic receptors and of [3H]prazosin to alpha 1-adrenoceptors in cortical membranes. In the presence of IC50 concentration (11 microM) of 1,3-di-o-tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor. These results indicate that sigma-compounds, at micromolar concentrations, inhibit muscarinic and alpha 1-adrenergic receptor-coupled phosphoinositide metabolism, probably through an interaction with the neurotransmitter recognition sites.

Animals↗
PubMed1990

Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats.

Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: 1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and 2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of [3H] inositol phosphates in [3H]inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats. Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of [3H]QNB (r2 = 0.627) and, particularly, with [3H]pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

[The effect of pesticides-CDM and AMZ on inhibition of the binding of 3H-clonidine to alpha 2-adrenoreceptor in rat forebrain tissue].

Chlordimeform (CDM) and Amitraz (AMZ) are two formamidine pesticides. CDM and AMZ inhibited the binding of 3H-Clonidine, 3H-Yohimbine to Alpha 2-adrenoreceptor of rat forebrain tissue in vitro with IC50 values of 62-68 mumol/L (CDM) and 95-110 mumol/L (AMZ). In vivo the administration of CDM and AMZ by ip showed the effect of inhibition on the binding and significant correlation of dose-effect r = 0.995 (CDM), 0.884 (AMZ). Time course test indicated that the lasting inhibition effect of CDM following exposure was shorter than AMZ. Similar results were observed with plasma in vitro. Comparing inhibition effects on rat forebrain tissue, directly induced by CDM and AMZ at different doses, with the results from the plasma of treated rats in vitro, there was a significant correlation r = 0.973 (CDM), 0.909 (AMZ). It showed that the inhibition effect of both CDM and AMZ was linked to the concentration of compounds chemical and their metabolites in blood. Time course and washing test indicated that the inhibition effect by CDM and AMZ was reversible.

Amidines↗
PubMed1989

Spectrophotometric assays for the enzymatic hydrolysis of the active metabolites of chlorpyrifos and parathion by plasma paraoxonase/arylesterase.

Human serum plasma paraoxonase/arylesterase exhibits a genetic polymorphism for the hydrolysis of paraoxon. One allelic form of the enzyme hydrolyzes paraoxon slowly with a low turnover number and the other(s) hydrolyzes paraoxon rapidly with a high turnover number. Chlorpyrifos-oxon, the active metabolite of the insecticide chlorpyrifos (Dursban), is also hydrolyzed by plasma arylesterase/paraoxonase. A specific assay for measuring hydrolysis of this compound is described. This assay is not subject to interference by the esterase activity of serum albumin. The Km for chlorpyrifos-oxon hydrolysis was 75 microM. Hydrolysis was inhibited by phenyl acetate, EDTA, and organic solvents. Enzyme activity required calcium ions and was stimulated by sodium chloride. Hydrolysis was optimized by using methanol instead of acetone to dissolve substrate. Unlike the multimodal distribution of paraoxonase, the distribution of chlorpyrifos-oxonase activity failed to show clear multimodality. An improvement in the assay for hydrolysis of paraoxon by plasma arylesterase/paraoxonase was achieved by elimination of organic solvents. Plotting chlorpyrifos-oxonase activity vs paraoxonase activity for a human population using the new assay conditions provided an excellent resolution of low activity homozygotes from heterozygotes for this allele. A greater than 40-fold difference in rates of chlorpyrifosoxon hydrolysis observed between rat (low activity) and rabbit sera (high activity) correlated well with the reported large differences in LD50 values for chlorpyrifos in these two animals, consistent with an important role of serum paraoxonase in detoxification of organophosphorus pesticides in vivo.

Acetone↗
PubMed1989

Acute and chronic effects of the pesticide amitraz on alpha 2-adrenoceptors in mouse brain.

There is increasing evidence to suggest that several effects of the formamidine pesticide amitraz (AMZ) in mammals are mediated by its interaction with alpha 2-adrenoceptors. AMZ has been shown to inhibit the binding of [3H]clonidine, a specific ligand for alpha 2-adrenoceptors to mouse brain in vitro and after administration in vivo. In the present study we have further investigated and characterized the effects of acute and chronic administration of AMZ on brain alpha 2-adrenoceptors in mice. AMZ caused a dose-dependent inhibition of [3H]clonidine binding. This inhibition was long-lasting (more than 48 h) following a relatively high dose of AMZ (75 mg/kg), while it was of short duration (2 h) following low doses (7.5 and 12.5 mg/kg). The time course of inhibition of [3H]clonidine binding was correlated with the plasma levels of AMZ and/or its active metabolites, measured with a novel radioreceptor binding technique. The alteration of [3H]clonidine binding was due to a decrease in alpha 2-adrenoceptor affinity, with no change in the density of binding sites, and was reversible in vitro upon repeated washing of the membrane preparation. Repeated administration of 7.5 mg/kg or 12.5 mg/kg AMZ, to yield a total dose of 75 mg/kg, showed no evidence of a cumulative effect on brain alpha 2-adrenoceptors.

Animals↗
PubMed1989

Effects of ethanol on muscarinic receptor-stimulated phosphoinositide metabolism during brain development.

The pattern of muscarinic receptor-stimulated inositol metabolism during postnatal development has a striking resemblance with the curve of rat brain growth spurt. Therefore, the enhanced hydrolysis of membrane inositol lipids by cholinergic agonists during this period may have a relevant role in cell proliferation and differentiation. In this study we have investigated whether exposure to EtOH to rat pups during the brain growth spurt, known to cause a permanent microencephaly, would alter muscarinic receptor-stimulated inositol metabolism in cerebral cortex. Female Long-Evans rats were administered 4 g/kg of EtOH, in two doses of 2 g/kg, by gastric intubation from postnatal day 4 to day 10. This treatment did not have any effect on the pups' body weight as compared to an equally handled, sucrose-fed group of animals. Blood EtOH concentration in the pups during exposure ranged between 237 and 283 mg/dl. Muscarinic receptor-stimulated inositol metabolism was measured in cerebral cortex slices of control and EtOH-treated rats at days 4, 7, 10, 12, 20 and 45 of age. Carbachol-induced accumulation of [3H] inositol phosphates was reduced significantly in EtOH-exposed animals on day 7 and 10, but not at other ages. This decrease was not due to an alteration of muscarinic receptor density or affinity. Exposure to EtOH had no effect on phosphoinositide metabolism stimulated by norepinephrine, serotonin or histamine in cerebral cortex, whereas the effect of glutamate was increased. Similar results were observed in the hippocampus. An identical treatment with EtOH in adult rats did not cause alteration in any of the biochemical parameters of the cholinergic system measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Interaction of the pyrethroid insecticides tetramethrin and cypermethrin with enteric cholinergic transmission in the guinea-pig.

In electrically-stimulated longitudinal muscle-myenteric plexus preparations of the guinea-pig ileum, the Type I pyrethroid insecticide tetramethrin (1-100 microM) caused a biphasic response consisting of an early transient increase followed by a sustained decrease in the amplitude of cholinergic contractions. The cholinergic potentiation was antagonized by phenytoin (3 microM), which also prevented the increase in twitch height caused by veratridine (30 nM). The late inhibitory effect of tetramethrin probably involved a direct action on the musculature since contractile responses to applied acetylcholine (100 nM) or histamine (300 nM) were also depressed by this compound. Cypermethrin (1-100 microM), a Type II pyrethroid, had only a minor enhancing effect on electrically evoked contractions. Cypermethrin (30, 60 microM), but not tetramethrin, antagonized the cholinergic response induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (1-100 microM). These results suggest that neural Na+ channels activation may underlie pyrethroid-induced potentiation of enteric cholinergic transmission. In small intestine, however, cypermethrin is also effective as a noncompetitive antagonist of GABA-A receptor mediated cholinergic contractions.

Animals↗
PubMed1988

Alpha 2-adrenoceptors as a target for formamidine pesticides: in vitro and in vivo studies in mice.

While the toxicity in insects of formamidines such as chlordimeform (CDM), its demethylated metabolite DCDM, and amitraz (AMZ) appears to involve activation of an octopamine-sensitive adenylate cyclase, their mechanism of action in mammals remains elusive. There is increasing evidence, however, that alpha 2-adrenoceptors might mediate certain effects of CDM, DCDM, and AMZ. In the present study, we investigated whether formamidines can interact directly with adrenoceptors in mouse forebrain both in vitro and after in vivo administration. Formamidines were potent inhibitors of the binding of [3H]clonidine to alpha 2-adrenoceptors with IC50's of 13 microM, 29 nM, and 130 nM for CDM, DCDM, and AMZ, respectively. Binding of [3H]yohimbine was inhibited with similar potencies. All compounds also inhibited with equal (CDM) or lower potency the binding of [3H]spiperone to dopamine D2 receptors and were weak inhibitors or inactive toward alpha 1- and beta-adrenoceptors, cholinergic muscarinic, GABAA, opiate mu, benzodiazepine, and histamine 1 receptors. Administration of formamidines to mice caused a dose-dependent decrease of [3H]clonidine binding. [3H]Clonidine binding returned to control values within 5 hr following administration of CDM and DCDM, but was still significantly decreased up to 48 hr after AMZ. Among different brain regions, [3H]clonidine binding was decreased to a larger extent in cerebral cortex, hippocampus, and midbrain. In vitro and ex vivo kinetic binding studies indicated that the effect of formamidines on alpha 2-adrenoceptors was due to a decrease in affinity and not to an alteration of the density of [3H]clonidine binding sites. The results of these biochemical studies support the hypothesis that alpha 2-adrenoceptors represent an important target for formamidine neurotoxicity in mammals.

Amidines↗
PubMed1988

Interactions of neurotoxicants with neurotransmitter systems.

Many neurotoxic compounds have been shown to interfere with neurotransmission both in vitro and following acute and chronic administration. Various parameters of neurotransmission can be directly affected by neurotoxicants; these include the enzyme(s) synthesizing a neurotransmitter, the release and uptake processes, the enzyme(s) which metabolize the neurotransmitter, the receptors, and post-synaptic events associated with receptor activation. Some neurotoxicants can interfere with neurotransmission indirectly, by interacting for example with energy metabolism, sodium channels or ATPases. Furthermore, measured alterations of any parameter of neurotransmission can be the result of neuronal death, due to a cytotoxic effect of the neurotoxicants. Chemicals which have been shown to alter neurotransmission include solvents (e.g. carbon disulfide), metals and organometals (e.g. lead, mercury, trimethyltin) and pesticides (e.g. organophosphates, pyrethroids, organochlorines, formamidines). An example of the various alterations in neurotransmitter parameters, which can occur following acute or chronic administration, is represented by the organophosphates. Organophosphorus insecticides owe their acute toxicity to inhibition of acetylcholinesterase and accumulation of acetylcholine at cholinergic receptors. Chronic exposure to these compounds results in the development of tolerance to their toxicity which is associated with a decrease in the density of muscarinic and nicotinic receptors in both the central and peripheral nervous system. Other examples of the interactions of neurotoxicants with neurotransmitters are also described.

Nervous System↗
PubMed1988

Spatial memory impairment and central muscarinic receptor loss following prolonged treatment with organophosphates.

Memory impairment is one of the recurrent complaints of agricultural workers repeatedly exposed to organophosphorus insecticides. In an effort to establish an animal model for such behavioral effects, which would allow studying its underlying biochemical mechanism(s), in this study we evaluated spatial memory in animals following repeated organophosphate exposure. Male Long-Evans rats were given daily i.p. injections of either diisopropylfluorophosphate (DFP; 1 mg/kg/day) or disulfoton (O,O-diethyl S-[2-(ethylthio)ethyl] phosphorodithioate; 2 mg/kg/day) for 14 days. Acetylcholinesterase activity was inhibited 71-77% in the cortex, hippocampus, and striatum of rats treated with DFP, and 73-74% in those treated with disulfoton. Binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cholinergic muscarinic receptors in the same brain areas was reduced 16-28% in organophosphate-treated rats. This decrease was due to a reduction in muscarinic receptor density (Bmax) with no changes in receptor affinity. At the end of the treatment rats were tested for spatial memory using the spontaneous alternation task in a T-maze. Rates of true spontaneous alternation were 64.4, 45.0, and 44.8% in animals which received corn oil, DFP, or disulfoton, respectively (P less than 0.05). These results indicate that prolonged inhibition of acetylcholinesterase caused by repeated organophosphate exposure alters spatial memory functions in rats, as well as causing a loss of muscarinic receptors. Considering the role of the cholinergic system in cognitive processes, these biochemical alterations could be related to the observed behavioral changes and may offer a potential explanation of the memory impairment reported by workers chronically exposed to organophosphates.

Acetylcholinesterase↗
PubMed1987

Interaction of the pesticide chlordimeform with adrenergic receptors in mouse brain: an in vitro study.

Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a formamidine insecticide acaricide whose major active metabolite is its N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal action in invertebrates appears to be related to activation of octopamine receptors, their mechanism of action in mammals has not been established. Because of similarities between octopamine and adrenergic receptors and suggestions of CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM with adrenoceptors were studied. In mouse brain membrane preparations CDM inhibited the binding of [3H]-clonidine to alpha 2- adrenoceptors and of [3H]-WB4101 to alpha 1-adrenoceptors with IC50 values of 18.2 and 87 microM, respectively. DCDM was a much more potent inhibitor, with IC50 values toward alpha 2-, and alpha 1-adrenoceptors of 44 nM and 1 microM, respectively. Both compounds were only weak inhibitors of the binding of [3H]-dihydroalprenolol to beta-adrenoceptors and of [3H]-quinuclidinyl benzilate to muscarinic receptors and were inactive toward benzodiazepines and gamma aminobutyric acid (GABAA) receptors. Inhibition of [3H]-clonidine binding by both compounds was competitive, as indicated by a decreased receptor affinity without changes in receptor density. Interaction of CDM and DCDM with [3H]-WB4101 binding, on the other hand, was more complex, and not of the competitive type. These results show that CDM and its metabolite DCDM can interact directly in vitro with alpha-adrenergic receptors, suggesting that these receptors could mediate some of the effects of CDM and DCDM in vivo.

Amidines↗
PubMed1987

Developmental changes in muscarinic receptor-stimulated phosphoinositide metabolism in rat brain.

Muscarinic receptor-stimulated phosphoinositide hydrolysis was investigated in rat brain during ontogeny by measuring the accumulation of [3H]inositol phosphates ([3H]InsPs) in cerebral cortex slices at various ages. Experiments with carbachol and acetylcholine showed that [3H]InsPs accumulation was maximal in 7-day-old rats (1477 +/- 98% of basal) and lowest in adult (75 days) rats (428 +/- 24% of basal). No differences were found in the EC50 values for both cholinergic agonists. This effect appeared to be mediated by the M1-muscarinic receptor subtype as it was blocked by pirenzepine with Ki = 29.1 +/- 7.1 nM (adults) and 87.9 +/- 18.2 nM (7-day-old rats). Incorporation of [3H]inositol into phospholipid decreased from day 3 to adulthood; however, when data of [3H]InsPs release were corrected for the incorporation at a given age, the highest stimulation by cholinergic agonists was still observed in 7-day-old rats. Among the other neurotransmitters tested (norepinephrine, histamine and serotonin), all known to stimulate phosphoinositide metabolism, none had the same developmental profile of [3H]InsPs accumulation as cholinergic agonists. In contrast to carbachol- and acetylcholine-stimulated phosphoinositide hydrolysis, the density of muscarinic binding sites, measured by [3H]quinuclidinyl benzilate binding, increased from day 3 to day 75. Acetylcholinesterase activity also increased during development. The dissociation of receptor binding sites from receptor-stimulated phosphoinositide metabolism suggests the presence of a more effective receptor-effector coupling at specific times of neonatal development, particularly 1 week. Furthermore, the fact that maximal stimulation of phosphoinositide hydrolysis coincides with the period of brain growth spurt in the rats suggests that this system in the cerebral cortex might be involved in the processes of cell division and differentiation.

Acetylcholine↗
PubMed1986

Effect of diethylmaleate and other glutathione depletors on protein synthesis.

The alpha, beta-unsaturated carbonyl compound diethylmaleate (DEM) depletes glutathione (GSH) from liver and other tissues, and for this reason it is often used in toxicological research to study the GSH-mediated metabolism of xenobiotics. In addition to GSH depletion, however, DEM has been shown to have other nonspecific effects, such as alteration of monooxygenase activities or glycogen metabolism. In this study we found that DEM (1 ml/kg) inhibited protein synthesis in brain and liver, following in vivo administration to mice. Protein synthesis was measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material. Administration of DEM also decreased body temperature by 2-3 degrees. By increasing the environmental temperature from 22 degrees to 35 degrees the hypothermic effect of DEM was prevented, without affecting its ability to deplete GSH from brain and liver. Furthermore, when mice were maintained at 35 degrees, DEM still caused a significant decrease in protein synthesis, suggesting that this effect was only partially due to hypothermia. To test whether inhibition of protein synthesis was related to GSH depletion, groups of animals were dosed with the alpha, beta-unsaturated carbonyl phorone (diisopropylidenacetone) or the specific inhibitor of GSH synthesis, buthionine sulfoximine (BSO). Phorone decreased GSH in liver and brain; however, it had no effect on protein synthesis. BSO decreased GSH levels in liver and kidney, but not in brain, and did not have any effect on protein synthesis in any of these tissues, nor did it cause any hypothermia. Furthermore, when hepatic GSH content was decreased by in vivo administration of DEM or BSO, there was no inhibition of protein synthesis measured in vitro. These results indicate that, at the dose normally used to deplete GSH from various tissues. DEM also exerts an inhibitory effect on protein synthesis, which appears to be only partially due to its hypothermic effect, and is independent from GSH depletion. BSO, which, in our experimental conditions, lacks this and other nonspecific effects, might be a good alternative for studies aimed at characterizing the role of GSH in the metabolism and toxicity of chemicals.

Animals↗
PubMed1986

Interaction of choline with muscarine receptor-stimulated phosphoinositide metabolism in the rat brain.

Previous receptor binding studies had shown that choline can interact with low potency with muscarine cholinoceptors. In the present study we have investigated whether choline is capable of functionally activating muscarine receptors by investigating its ability in stimulating the hydrolysis of phosphoinositides, a response believed to be coupled in brain to the M1 subtype of muscarine receptors. The results indicated that choline was only a very weak inducer of inositol phosphates (InsPs) accumulation in rat cerebral cortex slices as compared with acetylcholine or charbachol. Maximal increase of InsPs accumulation, at a choline concentration of 10 mM, was only 39 +/- 7%, as compared with the 4- to 6-fold stimulation induced by the other compounds. This effect of choline was not modified by physostigmine nor by the uptake inhibitor hemicholinium-3. At high concentrations, however, choline antagonized the stimulatory effect of acetylcholine and carbachol, suggesting that it might act as a partial agonist at this subtype of muscarine receptors, similar to what has been observed with oxotremorine. Choline had no effect on noradrenaline-stimulated InsPs accumulation.

Acetylcholine↗
PubMed1986

Inhibition of protein synthesis by trimethyltin.

The effects of trimethyltin chloride (TMT) on protein synthesis, measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material, were investigated in mice. One hour after intraperitoneal administration of a 3.0 mg/kg dose, TMT decreased brain protein synthesis by 47% and also caused a significant decrease (4.2 degrees C) in body temperature. When hypothermia was prevented by maintaining the animals at 35 degrees C, TMT decreased protein synthesis by 20%. Twenty-four hours following administration of TMT, protein synthesis was decreased in brain and liver; however, only a reduction of brain protein synthesis was observed at 48 hr. No hypothermia was present at either time point. A regional study in brain showed that at 24 and 48 hr after TMT administration, protein synthesis was decreased by 18-23% in cerebral cortex and hippocampus but not in cerebellum. TMT also inhibited protein synthesis in vitro in mouse brain homogenates with an IC50 of about 100 microM. Neither SnCl2, nor dimethyltin or monomethyltin had any effect on protein synthesis in vitro. These results suggest that, as for other neurotoxicants such as methyl mercury or acrylamide, inhibition of protein synthesis might be involved in TMT neurotoxicity.

Animals↗
PubMed1986

Cholinergic and opiate involvement in the antinociceptive effect of diisopropylfluorophosphate.

The organophosphate diisopropylfluorophosphate (DFP; 3 or 6 mg/kg, IP) caused a dose-related antinociception in mice which was antagonized by the muscarinic antagonist scopolamine. The opiate antagonist naloxone antagonized the antinociceptive effect of the highest dose of DFP, but did not affect the antinociception caused by 3 mg/kg DFP. Twenty-four hours after the administration of DFP, reaction time in animals which received a 3 mg/kg dose did not differ from control. However, reaction time was still significantly higher than control in mice administered 6 mg/kg DFP twenty-four hours earlier. This residual antinociception was antagonized by naloxone but not by scopolamine, suggesting that it was opioid in nature. These results suggest that antinociception induced by a low dose of DFP is primarily due to a cholinergic mechanism, while higher doses appear to affect also the opiate system. Since we have previously shown that DFP (6 mg/kg) increases met-enkephalin levels in brain, it is possible that high doses of DFP might interfere with enkephalin metabolizing enzymes. This conclusion cannot be extended to the organophosphate disulfoton, whose antinociception, even at high doses, appears to involve only an interaction with the cholinergic system.

Analgesics↗
PubMed1986

Conditioned taste aversion induced by organophosphate compounds in rats.

Three organophosphate compounds, dichlorvos, parathion and diisopropylfluorophosphate were tested as an unconditioned stimulus in the conditioned taste aversion (CTA) test. All organophosphates caused a dose-dependent CTA in rats at doses which did not induce any other signs of toxicity. Experiments with dichlorvos showed that the minimum dose which caused CTA did not alter the rats' sensitivity to pain or their behavior in either an open field or an inclined plane. Cholinesterase activity was inhibited in a dose-dependent manner in brain and plasma after administration of the organophosphates and CTA was correlated with the degree of plasma cholinesterase inhibition. CTA appears to be a sensitive indicator of neurobehavioral effects of mild exposure to organophosphates which causes only 30-40% inhibition of plasma cholinesterase.

Analgesics↗