Author/Editor		Sket, D; Čuček, D; Brzin, M
Title		Amphetamine-induced stereotyped behaviour in relation to subcellular localization of acetylcholinesterase in striatum of the rat
Type		članek
Source		Acta Pharm
Vol. and No.		Letnik 44, št. 3
Publication year		1994
Volume		str. 237-50
Language		eng
Abstract		The behavioural consequences of the irreversible inhibition of acetylcholinesterase (AChE) in the striatum, which is followed by a gradual restoration of its activity and subcellular distribution, was investigated. The biochemical-cytochemical findings were correlated with the concomitant alterations of amphetamine-induced stereotyped behaviour. Animals were pretreated with antidotes (atropine, diazepam and HI-6) and treated with a supralethal dose of soman, an irreversible inhibitor of AChE. Through pretreatment with atropine and diazepam, the muscarinic excitation and seizures were largely attenuated. In addition, peripheral AChE was partially protected with the oxime HI-6, contributing to the survival of the animals in spite of nearly total inhibition (98 per cent) of brain AChE. Behavioural analysis 24 hours after application of soman has shown that the inhibition of AChE had markedly prolonged (from 9.2 min to 20.8 min) the time interval between the injection of amphetamine (D-amphetamine sulphate, 5 mg kg-1 intraperitoneally) and the onset of amphetamine-induced stereotyped sniffing. During the subsequent gradual restoration of AChE activity, the prolongation of latent period was also gradually reversed and the time to the onset of stereotyped sniffing approached the control value in three to four days after poisoning. At that time only about 14-20 per cent of specific AChE activity was restored, measured in striatal homogenates. However, the time course analysis of the reappearance of AChE activity on distinct ultrastructural locations of the striatum has revealed th at the attenuation of the inhibitory effect on amphetamine-induced behaviour coincides with the restoration of AChE activity affiliated with the plasmalemma of dendrites. This observation suggests that subtle restoration of AChE on strategic intercellular location may be linked with the normalization of the stereotyped behaviour, rather than the recovery of total AChE activity.
Descriptors		CORPUS STRIATUM ACETYLCHOLINESTERASE BEHAVIOR, ANIMAL DEXTROAMPHETAMINE ANIMALS, LABORATORY RATS ATROPINE DIAZEPAM OXIMES SOMAN