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Behavioural responsiveness to amphetamine or scopolamine following repeated exposure to chlorphenvinphos in rats

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Gralewicz S., Lutz P., Tomas T.
Acta Neurobiologiae Experimentalis
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2002
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vol. 62
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issue 2
75-83
EN
A number of reports indicate that exposure to organophosphates (OPs), inhibitors of acetylcholinesterase (AChE), may result in long-lasting neurobehavioural alterations suggestive of an increased cholinergic tone. It is known that rats with cholinergic hyperreactivity are behaviourally hyposensitive to cholinergic antagonists and dopaminergic agonists.The purpose of the present study was to find out whether a similar trait would develop in rats exposed to chlorphenvinphos (CVP), an OP pesticide, in the past. The rats were given ten daily i.p. injections of CVP at doses of 0.5 mg/kg (group P-0.5) or 1.0 mg/kg (group P-1.0). The locomotion stimulating effect of i.p. injection of 1.0 mg/kg amphetamine (AMPH), or 0.7 mg/kg scopolamine (SCOP), was assessed on postexposure day 21 (group P-0.5) or 42 (group P-1.0), i.e. after a time sufficient for AChE recovery. The assessment revealed that in group P-1.0 the behavioural response to AMPH and SCOP was significantly depressed. In rats of the P-0.5 group, however, the behavioural response to each of the drugs was increased. The results suggest that, depending on the exposure level, contrasting alterations in some neurotransmitter systems may be induced by repeated exposure to CVP.
2
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Hyposensitivity to amphetamine following exposure to chlorphenvinphos - protection by amphetamine preexposure

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Gralewicz S., Lutz P., Szymczak W.
Acta Neurobiologiae Experimentalis
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2000
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vol. 60
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issue 2
203-207
EN
We investigated the effect of an acute exposure to chlorphenvinphos (CVP), an organophosphate anticholinesterase, on amphetamine-induced open-field locomotion in rats. CVP was administered in a single i.p. dose of 1.0 mg/kg (1/10 of the LD50). All animals were challenged with 1.0 mg/kg amphetamine (AMPH) three weeks after the CVP exposure, i.e. after a time sufficient for acetylcholinesterase recovery. Some rats were also given AMPH three weeks before the CVP exposure. In rats challenged with AMPH only once after the CVP exposure, AMPH- induced open-field locomotion was significantly reduced. Such an effect was not observed in rats given AMPH three weeks before the CVP exposure. The results suggest that a single CVP exposure may result in persistent dopaminergic hyposensitivity, and that an amphetamine pretreatment may protect the rat against this effect.
3
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The alimentary and social instrumental performance in dogs is suppressed by various doses of amphetamine

100%
Fonberg E., Jelen P.
Acta Neurobiologiae Experimentalis
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1993
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vol. 53
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issue 1
237-242
EN
Amphetamine was administrated intramuscularly 20-25 min before each experimental session in doses of: 0.2 mg/kg, 0.5 mg/kg and 1.0 mg/kg. Each dose was applied twice and preceded by a regular experimental sessions without any treatment. An instrumental performance consisted of alimentary-social differentation of two tones reinforced either by food or by sensory-social reward (petting by the experimenter). Amphetamine produced dose dependent decrease of the instrumental performance of both alimentary and social responses. This decrease was however not equal regarding both reactions. The dose of 1 mg/kg produced deep, statistically significant deterioration of alimentary as well as social responses. After the administration of the dose of 0.5 mg/kg the decrease of alimentary responses was equal to that produced by 1 mg/kg, whereas social responses was equal to that produced by 1 mg/kg, whereas social responses were less deteriorated. After the dose of 0.2 mg/kg the reduction of alimentary responses was smaller than produced by 0.5 mg/kg but still more pronounced than in the case of socially reinforced reactions. The results confirm our previous data that amphetamine suppresses positively motivated instrumental performance in dogs. The results also show that amphetamine-evoked suppression is dose dependent and that it is different for alimentary and social responses. This might indicate that the positive reward system is not homogenous but consists of some subsystems related to different kinds of reward. It is concluded that the suppressing effect of amphetamine is due to the inhibitory effect on motivation.
4
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Behavioral sensitization to amphetamine induced by a single i.p. dose of oxotremorine in the rat

100%
Gralewicz S.
Acta Neurobiologiae Experimentalis
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2002
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vol. 62
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issue 2
93-98
EN
Earlier experiments have revealed that rats treated with a single dose of chlorphenvinphos (CVP), an irreversible acetylcholinesterase inhibitor, are hyposensitive to amphetamine (AMPH) given three weeks after CVP. Exposure to CVP results in an excess of acetylcholine with subsequent overactivation of the nicotinic as well as muscarinic cholinergic receptors. The purpose of the present experiment was to find out whether a selective activation of muscarinic receptors could induce behavioral hyposensitivity to AMPH. To attain this purpose, male rats were pretreated once with 0. 00, 0.135, 0.27 or 0.55 mg/kg of oxotremorine, a muscarinic agonist, and challenged 15 days later with 1.0 mg/kg dose of AMPH. The pre- and postinjection open-field behavior of the rats was tested with the use of a computerized set of activity meters. The testing revealed that in oxotremorine pretreated animals the behavioral response to AMPH, i.e. increase in the ambulatory activity, was not diminished but, to the contrary, it was augmented. This effect was dose-dependent, being most pronounced in rats given the 0.55 mg/kg of oxotremorine. The possible cause of the difference between the effect of CVP and oxotremorine is discussed.
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