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
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.
