The influence of diazepam on atropine reversal of behavioural impairment in dichlorvos-treated rats.
Acute effects on the behaviour of the organophosphate insecticide dichlorvos and its standard antidotes possessing behavioural activity, atropine and diazepam, were studied separately and in combinations in male Wistar rats. In the spontaneous locomotor activity test, dichlorvos and diazepam decreased, whereas atropine increased performance. The effect of dichlorvos was obtained at a dose (5 mg/kg) that induced overt intoxication, and could not be reversed during first half hour-period after administration of any combination of drugs. In the other two tests, active avoidance learning and rotarod performance, the effective dose of dichlorvos (2 mg/kg) was devoid of somatic signs of intoxication. In these more sensitive tests, the effective atropine dose (40 mg/kg) completely reversed dichlorvos-induced incapacitation. In the rotarod test, diazepam (0.5 mg/kg) contributed to the incapacitating effect of dichlorvos, and impeded desirable influence of atropine as well. In the active avoidance test, diazepam (2.5 mg/kg) contributed to failure to escape; it did not influence the dichlorvos-induced decrease of avoidance performance, nor did it impair the completely reversing effects of atropine. The results point to the possible summation of acute incapacitating effects of organophosphates and diazepam on motor performance, which seems to be, at least partly, antagonized by sufficiently high doses of atropine. However, taking into account the long-term neuroprotective role of the anticonvulsant diazepam, and hence its delayed beneficial influences on behaviour, the immediate testing of atropine/diazepam treatment of organophosphate intoxication in active avoidance paradigm could possess beside sensitivity the predictive value as well.
Savić
Miroslav M
MM
Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, PO Box 146, Vojvode Stepe 450, 11221 Belgrade, Serbia and Montenegro. vukms@ptt.yu
Obradović
Dragan I
DI
Ugresić
Nenad D
ND
Bokonjić
Dubravko R
DR
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004006:Dichlorvos / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D018680:Cholinergic Antagonists; D007306:Insecticides; D001285:Atropine; D004006:Dichlorvos; D003975:Diazepam