Previous studies by our laboratory have shown that exposures to either lindane or dieldrin enhanced the rate of acquisition of the fully kindled amygdaloid seizure in the rat. To examine whether this enhancement generalizes to all groups of chlorinated hydrocarbon pesticides, the effect of dichlorodiphenyltrichloroethane (DDT) or chlordecone (kepone) was examined on the acquisition rate of the kindled amygdaloid seizure in the rat. Daily DDT exposure (5, 10 or 20 mg/kg, PO) failed to modify the rate of acquisition of the kindled amygdaloid seizure despite resulting in tremors in many of the rats in the high dose group. A single high dose of kepone (50 mg/kg) which resulted in up to 9 days of tremors and weight loss in the treated animals, also failed to modify the rate of kindling acquisition. These data demonstrate that not all CNS active chlorinated hydrocarbon pesticide exposures result in enhancement of kindling acquisition. The kindled amygdaloid seizure model of epilepsy appears to differentiate between the neurotoxic consequences of chlorinated hydrocarbon pesticides that cause myoclonus and seizures (e.g., lindane and dieldrin) and those that primarily cause tremors (DDT and kepone).

Amygdala↗

PubMedDate not supplied

Effects of hexachlorocyclohexane isomers on the acquisition of kindled seizures.

The effects of three isomers (alpha, beta, gamma) of hexachlorocyclohexane on the acquisition and expression of kindled amygdaloid seizures were compared. Treatment with corn oil (vehicle) was compared with daily 5 mg/kg doses of the isomers for 15 days during kindling procedures. The results confirmed the proconvulsant action previously described for the gamma-HCH isomer (lindane). Alpha-HCH did not produce significant effects. Rats treated with beta-HCH exhibited delayed rates of kindling acquisition and less severe seizures. Exposure to beta-HCH (5, 10 and 20 mg/kg) daily produced a dose-dependent decrease in the rate of kindling acquisition, seizure severity and afterdischarge duration. The differences were still manifest during an additional 20 kindling trials after beta-HCH administration had stopped. It is concluded that significant differences exist among the isomers of HCH with respect to their effects on the mammalian central nervous system and their effect in the kindling model of epilepsy. The availability of stereoisomers possessing different actions on kindling should make these compounds useful for discriminating between non-specific changes induced in membranes or at binding sites and specific changes correlated with proconvulsant or anticonvulsant effects in the kindling model.

Amygdala↗

PubMedDate not supplied

Effects of lindane on excitation and inhibition evoked in dentate gyrus by perforant path stimulation.

Lindane, 10 mg/kg, IP in DMSO, was administered to rats implanted with electrodes to stimulate the perforant path and record from the dentate gyrus of the hippocampal formation. Dentate responses were examined in acutely prepared, anesthetized rats and chronically prepared rats in unanesthetized and anesthetized states. The most significant and reliable effect of lindane administration was to increase the number of granule cells excited to discharge in response to perforant path stimulation. Further analysis indicated that lindane did not appear to produce this action by increasing transmitter release from the perforant path terminals. The primary site of action was the granule cell itself. Inhibition, mediated by recurrent collaterals and believed to be GABA-mediated, was not reduced and, in some circumstances, was increased after lindane administration. These data suggest that the primary action of lindane in intact subjects is to increase neuronal excitability. Enhanced transmitter release or reduction in GABA-mediated inhibition could not be demonstrated to contribute significantly to this effect.

Anesthesia, General↗

PubMedDate not supplied

Proconvulsant effects of lindane: enhancement of amygdaloid kindling in the rat.

Rats receiving daily oral administrations of lindane were kindled using daily amygdaloid stimulation. In naive rats lindane exposure increased the probability of evoking an afterdischarge and increased the probability that a convulsive response would be associated with the afterdischarge. During kindling lindane increased the rate of acquisition of the fully kindled state. Lindane exposed rats required fewer stimulations, fewer afterdischarges and fewer seconds of afterdischarge to kindle. The final kindled state, however, was not modified by lindane exposure. The effects of lindane on kindling were directly proportional to exposure. A log-linear regression of the data estimated the minimal effective exposure level to be about 0.5 mg/kg/day lindane. Brain concentrations at this exposure were about 0.5 microgram/g, while blood levels were near 0.1 microgram/ml. The kindled seizure model appears to be a useful tool for estimating exposures at which certain neurotoxic responses emerge.

Amygdala↗

PubMedDate not supplied

Mode of action of lindane, dieldrin and related insecticides in the central nervous system.

A mode of action for lindane, dieldrin and related chlorinated hydrocarbon insecticides is proposed. The available evidence suggests that these insecticides act upon neurons in a global manner. Their primary target is the synapse, and they act there to intensify synaptic activity, primarily by enhancing transmitter release from the presynaptic terminal. All neurons appear to be affected. There is no apparent predilection for excitatory or inhibitory systems in the nervous system nor is there evidence for a specific action upon a single neurotransmitter or neurotransmitter system. It is proposed that the modifications that occur in behavior are based upon this same mode of action. A simplified model of brain plasticity, the kindled seizure model, is described as a potential tool for further investigation.

Animals↗

PubMedDate not supplied

Proconvulsant action of lindane compared at two different kindling sites in the rat--amygdala and hippocampus.

Lindane facilitates the rate of acquisition of a maximal kindled amygdaloid response (MKAR) in rats. We tested whether this is a site specific effect or a more generalized one by comparing acquisition of MKAR and of the maximal kindled hippocampal response (MKHR). The hippocampus was chosen for comparison because acquisition of MKHR requires 2-3 times more trials than does acquisition of MKAR. Rats were implanted with electrodes in amygdala or hippocampus and exposed to either 0 or 5 mg/kg/day lindane, orally, throughout the acquisition period. Lindane exposure reduced the number of trials needed to acquire MKAR and MKHR to the same extent, 70 +/- 5 and 69 +/- 11% of control rats, respectively. However, the specifics of the facilitation varied between sites. The facilitation of amygdaloid kindling acquisition was associated with an increase in the length of afterdischarge (AD) produced on each trial. The cumulative seconds of AD (CSAD) accrued by amygdaloid rats given lindane was the same (95 +/- 15%) as control rats. During hippocampal kindling lindane exposure reduced AD durations. The facilitation of hippocampal kindling was associated with a reduction in total AD experience. Hippocampal rats given lindane accrued only 52 +/- 7% of the CSAD accrued by control rats.

Amygdala↗