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mise à jour du
29 août 2010
Gen. Pharmac.
1994;25(6):1263-1267
Effects of Carbaryl on some Dopaminergic Behaviors
in Rats
  
A. R. Rigon, M. Reis, R. N. Takahashi
Departamento de Farmacologia, Centro Ciéncias Biolôgicas, Universidade Federal Santa Catarina, Florianopolis, Brasil

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Abstract
1. The effects of acute oral administration of carbaryl (10-80 mg/kg), a carbamate insecticide, on some experimental models for detecting dopaminergic activity were examined in rats. Also, serum biochemical variables following carbaryl treatments were determined.
 
2. Carbaryl (20 and 40 mg/kg) significantly increased the number of apomorphine-induced yawns and at dose of 80mg/kg it prolonged the duration time of haloperidol-induced catalepsy. Pretreatment with carbaryl failed to affect apomorphine-induced stereotypes.
 
3. Carbaryl significantly reduced blood cholinesterase activity and elevated blood glucose levels and SGOT and SGPT activities.
 
4. These results indicate that low oral doses of carbaryl can cause behavioral and toxicological effects in rats.

INTRODUCTION
 
Carbaryl (l-naphthyl-N-methylcarbamate) is extensively used as an agricultural and as a home insecticide. Carbaryl's primary action is believed to involve a rapid and brief inhibition of acetylcholinesterase (AchE) activity (Reiner et al., 1967). In a previous study by our group (Takahashi et al., 1991), behavioral changes such as decreased locomotor activity, increased threshold to thermic stimuli, increased duration of haloperidol-induced catalepsy, as well as a hypothermie effect correlated with a reduction in blood cholinesterase activity, were observed in rats following acute exposure to carbaryl. Carbaryl has also been shown to induce a dose-dependent increase of tremors in rats (Ray and Poddar, 1990). In addition, these authors have demonstrated that central dopaminergic mechanisms are involved in the carbaryl-induced tremor (Ray and Poddar, 1985). Since it is well known that a balance between dopaminergic and cholinergic activities within the striatum is essential for normal motor function (Bartholini et al., 1975; Carry and De Veaugh-Geiss, 1982), the present study was designed to further characterize the effects of carbaryl on some experimental rat models believed to involve dopaminergic mechanisms. Further, biochemical variables following AchE treatments were determined.
 
DISCUSSION
 
The present results suggest that, single administration of low doses of carbaryl by oral route can alter some behavioral responses involving dopaminergic mechanisms and can cause acute toxicity in rats. Thus, the finding that carbaryl enhances apomorphine-induced yawnings and haloperidol-induced catalepsy coincident with increases in blood glucose levels, elevated SGOT, SGPT activities and inhibition of blood ChE activities in rats confirms and extends previous studies pointing to a central cholinergic-dopaminergic interaction on some behavioral responses to carbaryl (Ray and Poddar, 1985; Takahashi et al., 1991).
 
The salient finding of the present study was that carbaryl, within the range of doses with little or no effect per se on yawning or catalepsy responses, induced a typical bell-shaped effect in the mean number of apomorphine-induced yawns and potentiated the duration of haloperidol-induced catalepsy. It is well known that yawning behaviour can be induced in rats by systemic administration of very small doses of apomorphine or other dopaminergic agonists (Mogilnicka and Klimek, 1977) and cholinergic agofists (Yamada and Furukawa, 1980). Regarding the catalepsy test, it is known that the extrapyramidal effects produced by neuroleptic drugs, like haloperidol, in animals are related to a blockade of postsynaptic dopaminergic receptors in the striatum (Baldessarini, 1980).
 
Since both responses are believed to be a behavioural consequence of the involvement of dopaminergic and cholinergic systems (Yamada and Furukawa, 1980; Coyle and Campochiaro, 1976) and assuming that carbaryl has negligible effects on dopaminergic receptors, it is likely that excessive cholinergic activity produced by carbaryl may account for the potentiation of yawning and catalepsy. In this context, it is noteworthy that Ray and Poddar (1985) reported a significant reduction ofthe carbaryl-induced tremor by prior treatment of rats with L-DOPA, while haloperidol significantly exacerbated this response. The lack of a significant antistereotypic effect of carbaryl on apomorphinetreated rats in the present study can be explained in terms of the dose-response relationship for carbaryl. It is important to emphasize that in our study the highest dose of carbaryl employed was 80 mg/kg, whereas a higher dose of the drug (200 mg/kg) was used by Ray and Poddar (1985).
 
Additional evidence to the contention that carbaryl-induced effects are primarily cholinergic comes from our toxicological data showing reduced blood ChE activity and enhanced blood glucose levels in carbaryl-treated rats. Indeed, several reports have consistently described that some behavioral effects induced by carbaryl appear to be related to changes in the ChE activities (Elawar et al., 1988; Kobayashi et al., 1985, 1988; Ruppert et al., 1983; Takahashi et al., 1991). The finding that carbaryl induced hyperglycemia in experimental animals is also consistent with the reports that glucose concentration increases in acute poisoning with organophosphorus compounds (Lukaszewicz-Hussain et al., 1985).
 
Moreover, it has been reported that stimulation of the brain cholinoceptive neurons produces hyperglycemia (Ramu and Korner, 1975; Korner and Ramu, 1979; Iguchi et al., 1990). Overall, these effects on glucose levels are supported by the recent finding showing that neostigmine injected icy, induces hyperglycemia mediated by central muscarinic receptors in rats (Iguchi et al., 1990). The observation that, even after the administration of low doses of carbaryl, SGPT and SGOT activities were elevated is interesting. This fact suggests that, despite the supposed low toxicity of carbaryl in mammals, the hepatic function in rat was affected by acute exposure to carbaryl.
 
In conclusion, these results show that low oral doses of carbaryl can induce behavioral and toxicological effects in rats and that some of these effects appear to be centrally mediated, involving the balance between cholinergic and dopaminergic systems.