Abstract
Pretreatment of rats with phenoxybenzamine (5 mg/kg; SC), an alpha adrenergic antagonist, decreased the peak tremor power and startle magnitude of rats subsequently given DDT (75 mg/kg; PO) or chlordecone (60 mg/kg; IP), without having a significant effect on control animals. Pretreatment with an intracerebroventricular injection of calcium (3.75 μM in 5 μl NaCl) decreased the peak tremor power due to subsequently administered DDT, while increasing the tremor response in rats later dosed with chlordecone. The effects of phenoxybenzamine are postulated to be due to a blockade of an excitatory influence of the adrenergic system. Calcium may decrease DDT-induced tremor by acting as a neuronal stabilizer. Potentiation of the tremorigenic effect of chlordecone by calcium may be due to increased levels of intracellular calcium, resulting in augmented release of neurotransmitters in chlordecone-exposed animals.
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References
Blaustein MP (1979) The role of calcium in catecholamine release from adrenergic nerve terminals. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon, New York
Chen PH, Tilson HA, Marbury GD, Karoum F, Hong JS (1985) Effect of chlordecone (Kepone) on the rat brain concentration of 3-methoxy-4-hydroxyphenylglycol: Evidence for a possible involvement of the norepinephrine system in chlordecone-induced tremor. Toxicol Appl Pharmacol 77(1):158–164
Davis M (1980) Neurochemical modulation of sensory motor reactivity: Acoustic and tactile startle reflexes. Neurosci Biobehav Rev 4:241–263
Davis M, Astrachan DI (1981) Spinal modulation of acoustic startle: Opposite effects of clonidine and d-amphetamine. Psychopharmacology 75:219–225
Davis M, Gendelman DS, Tischler MD, Gendelman PM (1982) A primary acoustic startle circuit: Lesion and stimulation studies. J Neurosci 2(6):791–805
Desaiah D (1981) Interaction of chlordecone with biological membranes. J Toxicol Environ Health 8(5–6):719–730
End DW, Carchman RA, Dewey WL (1981) Neurochemical correlates of chlordecone neurotoxicity. J Toxicol Environ Health 8(5–6):707–718
Ferris RM, White HL, Cooper BR, Maxwell RA, Tang FLM, Beaman OJ, Russel A (1981) Some neurochemical properties of a new antidepressant, bupropion hydrochloride (Wellbutrin). Drug Dev Res 1:21–35
Fielding S, Lal H (1981) Clonidine: New research in psychotropic drug pharmacology. Med Res Rev 1(1):97–123
Frankenhaeuser B, Hodgkin AL (1957) The action of calcium on the electrical properties of squid axons. J Physiol 137(2):218–224
Gerhart JM, Hong JS, Uphouse LL, Tilson HA (1982) Chlordecone-induced tremor: Quantification and pharmacological analysis. Toxicol Appl Pharmacol 66:234–243
Gerhart JM, Hong JS, Tilson HA (1983) Studies on the possible sites of chlordecone-induced tremor in rats. Toxicol Appl Pharmacol 70:382–389
Goldberg MR, Robertson (1983) Yohimbine: A pharmacological probe for study of the α2-adrenoceptor. Pharmacol Rev 35(3):143–180
Greengrass P, Bremner R (1979) Binding characteristics of 3H-prazosin to rat brain α-adrenergic receptors. Eur J Pharmacol 55(3):323–326
Hayes WJ Jr (1959) Pharmacology and Toxicology of DDT. In: Mueller P (ed) DDT, the insecticide dichlorodiphenyltrichloroethane and its significance. Volume 2, Birkhäuser, Basel, pp 11–247
Herr DW, Tilson HA (1986) Catecholaminergic modulation of 1,1,1-trichoro-2,2-bis(p-chlorophenyl)ethane (DDT)-induced tremor. Toxicologist 6:221
Herr DW, Hong JS, Tilson HA (1985) DDT-induced tremor in rats: Effects of pharmacological agents. Psychopharmacology 86(4):426–431
Hille B (1968) Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol 51(2):221–236
Hong JS, Tilson HA, Uphouse LL, Gerhart J, Wilson WE (1984) Effects of chlordecone on brain neurotransmitters: Possible involvement of the serotonin system in chlordecone-elicited tremor. Toxicol Appl Pharmacol 73:336–344
Hrdina PD, Singhal RL, Peters DAV, Ling GM (1973) Some neurochemical alterations during acute DDT poisoning. Toxicol Appl Pharmacol 25:276–288
Hrdina PD, Singhal RL, Ling GM (1975) DDT and related chlorinated hydrocarbon insecticides: Pharmacological basis of their toxicity in mammals. Adv Pharmacol Chemother 12:31–88
Hudson PM, Chen PH, Tilson HA, Hong JS (1985) Effects of p,p′-DDT on the rat brain concentrations of biogenic amine and amino acid neurotransmitters and their association with p,p′-DDT-induced tremor and hyperthermia. J Neurochem 45(5):1349–1355
Hwang EC, Van Woert MH (1978) p,p′-DDT-induced neurotoxic syndrome: Experimental myoclonus. Neurology 28:1020–1025
Jordan JE, Grice T, Mishra SK, Desaiah D (1981) Acute chlordecone toxicity in rats: A relationship between tremor and AT-Pase activities. Neurotoxicology 2(2):355–364
Joy RM (1982) Chlorinated hydrocarbon insecticides. In: Ecobichon DJ, Joy RM (eds) Pesticides and neurological diseases. CRC Press, Boca Raton, Fla, pp 91–150
Komulainen H, Bondy S (1987) Modulation of levels of free calcium within synaptosomes by organochlorine insecticides. J Pharmacol Exp Ther (in press)
MacDonald RL (1983) Barbiturate and hydantoin anticonvulsant mechanisms of action. In: Basic mechanisms of neuronal hyperexcitability. Liss, New York, pp 361–387
Matsumura F, Narahashi T (1971) ATPase inhibition and electrophysiological change caused by DDT and related neuroactive agents in lobster nerve. Biochem Pharmacol 20(4):825–837
Miller RG (1966) Simultaneous statistical inference. McGraw-Hill, New York
Murphy SD (1980) Pesticides. In: Doull J, Klaassen CD, Amdur MO (eds) Casarett and Doull's Toxicology, the basic science of poisons, 2nd edition. McMillan, New York, pp 357–408
Narahashi T (1982) Cellular and molecular mechanism of action of insecticides: Neurophysiological approach. Neurobehav Toxicol Teratol 4(6):753–758
Peterson BW, Pitts NG, Fukushima K (1979) Reticulospinal connections with limb and axial motorneurons. Exp Brain Res 36(1):1–20
Pryor GT, Uyeno ET, Tilson HA, Mitchell CL (1983) Assessment of chemicals using a battery of neurobehavioral tests: A comparative study. Neurobehav Toxicol Teratol 5:91–117
Reiter LW, Kidd K, Ledbetter G, Gray LE, Chernoff N (1977) Comparative behavioral toxicology of Mirex and Kepone in the rat. Toxicol Appl Pharmacol 41(1):143
Rubin RP (1974) Calcium and the secretory process. Plenum, New York
Schramm M, Towart R (1985) Minireview: Modulation of calcium channel function by drugs. Life Sci 37(20):1843–1860
Taylor JR (1982) Neurological manifestations in humans exposed to chlordecone and follow-up results. Neurotoxicology 3(2):9–15
Tilson HA, Hong JS, Mactutus CF (1985) Effects of 5,5-diphenylhydantoin (Phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin. J Pharmacol Exp Ther 233(2):285–289
Tilson HA, Hong JS, Gerhart JM, Walsh TJ (1987) Animal models in neurotoxicology: The neurobehavioral effects of chlordecone (Kepone). In: Thompson T, Dews P, Barrett J (eds) Advances in behavioral pharmacology. Erlbaum, New York (in press)
White SR, Neuman RS (1980) Facilitation of spinal motorneurone excitability by 5-hydroxytryptamine and noradrenaline. Brain Res 188(1):119–127
Winer BJ (1962) Statistical principles in experimental design. McGraw-Hill, New York
Woolley DE (1982) Neurotoxicity of DDT and possible mechanisms of action. In: Prasad K, Vernakis A (eds) Mechanisms of action of neurotoxic substances. Raven, New York, pp 95–141
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Herr, D.W., Gallus, J.A. & Tilson, H.A. Pharmacological modification of tremor and enhanced acoustic startle by chlordecone and p,p′-DDT. Psychopharmacology 91, 320–325 (1987). https://doi.org/10.1007/BF00518184
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DOI: https://doi.org/10.1007/BF00518184