Evaluation of sensory evoked potentials in Long Evans rats gestationally exposed to mercury (Hg0) vapor.

Mercury is known to alter neuronal function and has been shown to cross the placental barrier. These experiments were undertaken to examine if gestational exposure to mercury vapor (Hg(0)) would result in alterations in sensory neuronal function in adult offspring. Dams were exposed to 0 or 4 mg/m(3) Hg(0) for 2 h/day from gestational days 6-15. This exposure paradigm has been shown to approximate a maximal tolerated dose of Hg(0) for the dams. Between postnatal days 140-168, male and female offspring (one of each gender/dam) were examined using a battery of sensory evoked potentials. Peripheral nerve action potentials, nerve conduction velocity, somatosensory evoked responses (cortical and cerebellar), brainstem auditory evoked responses, pattern evoked potentials, and flash evoked potentials were quantified. Gestational exposure to 4 mg/m(3) Hg(0) did not significantly alter any of the evoked responses, although there was a suggestion of a decrease in compound nerve action potential (CNAP) amplitudes in male animals for the 3 mA stimulus condition. However, this possible change in CNAP amplitudes was not replicated in a second experiment. All evoked potentials exhibited predictable changes as the stimulus was modified. This shows conclusively that the evoked responses were under stimulus control, and that the study had sufficient statistical power to detect changes of these magnitudes. These results indicate that gestational exposure to 4 mg/m(3) Hg(0) did not result in changes in responses evoked from peripheral nerves, or the somatosensory, auditory, or visual modalities.     

Four Weeks' Inhalation Exposure of Long Evans Rats to 4‐tert‐Butyltoluene: Effect on Evoked Potentials,Behaviour, and Brain Neurochemistry

Long‐lasting central nervous system (CNS) neurotoxicity of 4‐tert‐butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight‐arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure‐free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5‐hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long‐lasting effects may cause or reflect TBT‐compromised CNS function.     

Function of the Auditory and Visual Systems,and of Peripheral Nerve,in Rats after Long-Term Combined Exposure to n-Hexane and Methylated Benzene Derivatives. I. Toluene

Rats were exposed to n-hexane, toluene, or toluene together with n-hexane, each solvent 1000 p.p.m. (1000+ 1000 p.p.m. in combined exposure), 21 hr/day, 7 days/week during 28 days. Neurophysiological recordings were made 2 days, 3 months, and one year after end of exposure. A reduction in auditory sensitivity, recorded by click evoked auditory brainstem response, was observed 2 days after exposure to toluene alone, or to toluene together with n-hexane, but not after exposure to n-hexane alone. The reduction lasted one year after the exposure. Three months after combined exposure, a synergistic enhancement of loss of auditory sensitivity was observed in the mixed exposure group. One amplitude in the flash evoked potentials was lowered in the n-hexane exposed group 2 days after exposure. No such reduction was seen after simultaneous exposure to toluene. Exposure to n-hexane alone caused a marked decrease in peripheral nerve conduction velocity 2 days and 3 months after exposure, while exposure to n-hexane together with toluene had only a small effect on this velocity.     

Immunological Changes Produced in Rats by Prenatal Exposure to Carbon Monoxide

Abstract: Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O₂^- release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.     

Function of the Auditory and Visual Systems,and of Peripheral Nerve,in Rats after Long-Term Combined Exposure to n-Hexane and Methylated Benzene Derivatives. II. Xylene

Rats were exposed to xylene, to n-hexane. or to xylene together with n-hexane, each solvent 1000 p.p.m. (1000+1000 p.p.m. in mixed exposure), 18 hr/day, 7 days/week during 61 days. Neurophysiological recordings were made 2 days, 4 months, and 10 months after the end of exposure. Exposure to n-hexane alone, or xylene alone, caused a slight loss of auditory sensitivity as recorded by auditory brainstem response 2 days after the exposure. Exposure to n-hexane together with xylene caused persistent loss of auditory sensitivity (7-17 dB; P<0.05) which was non-additively enhanced (P<0.01). The latencies of the flash evoked potentials in the group exposed to n-hexane alone were prolonged (re C group) 2 days after exposure, while smaller prolongations were found in the group exposed to xylene together with n-hexane. Exposure to n-hexane alone caused a marked decrease in nerve conduction velocity, while simultaneous exposure to xylene inhibited n-hexane-induced velocity reduction in peripheral nerve (P<0.01).     

Neurophysiological Consequences of Acute Exposure to Methylpyridines

Neurophysiological Consequences of Acute Exposure to Methylpyridines.DYER, R. S., BURDETTE, L. J., JANSSEN, R., AND BOYES, W. K.(1985). Fundam. Appl. Toxicol.. 5,920-932. A series of neurophysiologicaltests was performed on Long-Evans hooded rats treated with either2-, 3-, or 4-methylpyridine at dosages of 100 mg/kg, approximatelyone-half the ip LD50. The tests contained measures of sensoryfunction (paired pulse flash evoked potentials, pattern reversalevoked potentials, and brainstem auditory evoked responses)and cerebral excitability (pentyl-enetetrazol seizures and hippocampalafterdischarges). In general, rats treated with 2- and 3-methylpyridinewere more affected than those treated with 4-methylpyridine.The changes observed were in many ways similar to those seenfollowing administration of depressant compounds: increasedlatency of evoked potentials and increased latency to PTZ seizures.Not all findings, however, were consistent with previously observedpatterns of central nervous system depression.     

Four weeks' inhalation exposure of Long Evans rats to 4-tert-butyltoluene: effect on evoked potentials, behaviour, and brain neurochemistry

Long-lasting central nervous system (CNS) neurotoxicity of 4-tert-butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function.     

Carbon monoxide and flash evoked potentials from rat cortex and superior colliculus

In view of the conflict between qualitative reports that flash evoked potentials from superior colliculus (SC) and visual cortex (VC) of rats are uniquely sensitive to low levels of carbon monoxide (CO), and a more quantitative report that the visual cortex evoked potential is not sensitive to low levels of CO, the present report documents the effects of different concentrations of CO upon flash evoked potentials from these areas. The amplitude of the P3-N4 component from the SC evoked potential demonstrated the best dose/effect relationship, increasing up to levels of 38% carboxyhemoglabin (COHb). Latencies were affected only when COHb levels reached 55%. The use of the visual system to determine effects of toxic agents upon the central nervous system is discussed.     

Neurobehavioral effects of dietary restriction in rats

The effects of reduced body weight gain on nervous system function of young male Fischer 344 rats were examined. The rats were fed 15% ('mild') or 50% ('severe') less than the controls. Mild and severe dietary restriction resulted in 9% and 38% lower body weight compared to the controls. Mild dietary restriction caused slight changes in flash evoked potentials, auditory brainstem responses, caudal nerve action potentials, and body temperature. Severe dietary restriction increased the magnitude of the effects noted in the mild group, as well as causing a significant decrease in grip strength. Somatosensory evoked responses were not affected by either mild or severe restriction. Diet restricted rats were more excitable while restrained for testing. Thus, dietary restriction has significant effects on numerous behavioral and neurophysiological parameters that should be considered in the interpretation of neurotoxicological data when body weight differences are present.     

INHALATION TOXICITY OF 4-ETHOXYANILINE (p -PHENETIDINE): CRITICAL ANALYSIS OF RESULTS OF SUBACUTE INHALATION EXPOSURE STUDIES IN RATS

This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p -phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p -phenetidine/m 3 using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m 3. In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m 3 as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m 3 and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m 3 and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m 3 and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m 3 and a hepatic hemosiderosis only at 882.6 mg/m 3. These data suggest that the toxicity of p -phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m 3 and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m 3 air and that of the 1-wk study was 38.2 mg/m 3 air. This difference in NOAELs is considered to be related to the selection of exposure concentrations rather than cumulative toxicity.     

Alterations in Rat Flash and Pattern Reversal Evoked Potentials after Acute or Repeated Administration of Carbon Disulfide (CS2)

Because solvents may selectively alter portions of visual evokedpotentials, we examined the effects of carbon disulfide (CS₂)on flash (FEPs) and pattern reversal (PREPs) evoked potentials.Long-Evans rats were administered ip carbon disulfide eitheracutely or for 30 days. FEPs or PREPs were recorded prior toand 1, 2, 4, 8, or 24 hr alter a single dose of CS₂ (0, 100,200, 400, or 500 mg/kg). Flash evoked potentials were also recorded1, 2, 6, and 24 hr after the last of 30 doses of 200 mg CS₂/kg/day.Acute exposure to CS₂ consistently decreased the amplitude ofFEP peak N₁₆₀ at 1 hr, depressed peak N₃₀ amplitude over 2–4hr, and increased the latency of peaks P₂₁, N₃₀, P₄₆, N₅₆, andN₁₆₀ for up to 4 hr alter treatment. Carbon disulfide decreasedthe amplitude of PREP peaks P₆₅, N₈₃, P₈₈, and N₁₂₂ 4 hr altertreatment. Colonic temperature was depressed up to 8 hr altertreatment. Administration of 200 mg CS₂/kg/day decreased theamplitude of FEP peak N₃₀ and increased the latencies of peaksP₂₁, N₃₀, P₄₆, N₅₆, and N₁₆₀ up to 24 hr alter the last dose.The differential effects of CS₂ on portions of FEPs indicatethat FEP peaks can be independently modulated. Changes in PREPswere temporally correlated with alterations in early FEP peaks,but FEP peak N₁₆₀ was depressed at an earlier time point. RepeatedCS₂ exposure affected FEPs at lower doses and for a longer timethan an acute exposure, similar to the reported greater severityof neurological disturbances following repeated CS₂ exposuresin humans.     

Neurotoxic properties of musk ambrette

Musk ambrette (2,6-dinitro-3-methoxy-4-tert-butyltoluene), a nitro-musk compound widely used as a fixative in fragrance formulations and found to a lesser degree in flavor compositions, produces hindlimb weakness when administered in the diet or applied to skin of rats for periods up to 12 weeks. Underlying neuropathologic changes consist of primary demyelination and distal axonal degeneration in selected regions of the central and peripheral nervous system. Murine neurological disease induced by musk ambrette occurs at doses well above estimated maximum daily human exposure. Lifetime experimental neurotoxicology studies using lower concentrations of musk ambrette for prolonged periods would be needed for the estimation of human risk.     

Prenatal Toxicity of Xylene Inhalation in the Rat: A Teratogenicity and Postnatal Study

Technical xylene (cas.nr. 1330-20-7) was investigated for development toxicity in a teratology and in a postnatal study. Rats (Mol: WIST) were exposed to 500 p.p.m. 6 hr per day on days 4 to 20 of gestation. There were no signs of maternal toxicity. In the teratology study, no exposure-related differences were found except for delayed ossification of os maxillare. In the postnatal study, the xylene-exposed pups had a higher body weight and an impaired performance on a motor ability test (Rotarod). Due to the possibility of direct toxic effects of xylene on the developing central nervous system, further studies are needed to investigate dose-effect relationship for this type of effects.     

Function of the Auditory System,the Visual System,and Peripheral Nerve and Long-Term Combined Exposure to Toluene and Ethanol in Rats

Abstract: Male pigmented rats (n=36) were exposed to toluene and/or ethanol (1000 p.p.m. toluene in the inhaled air 21 hr/day, and 5.7-8.0% ethanol in the drinking water continuously) during 8 weeks. Electrophysiological recordings were made 1 week after the exposure. Auditory sensitivity (auditory brainstem response) was reduced only after exposures including toluene. At 20 kHz, ethanol antagonized toluene-induced loss of auditory sensitivity (P<0.05). Flash evoked potentials were not affected in any group. In peripheral nerve, exposures containing ethanol were followed by increased amplitudes of nerve and muscle action potentials. Exposures including toluene were followed by an increase in liquid consumption.     

Four Weeks Inhalation Exposure to n-Heptane Causes Loss of Auditory Sensitivity in Rats

Abstract: The effects of exposure to 800 or 4000 p.p.m. of n-heptane, CAS No. [142-82-5]) 6 hr per day during a period of 28 days, on the function of the auditory system were examined by measurements of auditory brain stem response (ABR) in Long Evans rats. The ABR was measured simultaneously with both needle electrodes and implanted electrodes. The wave forms recorded with the two types of electrodes were similar, but the amplitudes were largest on the recordings with implanted electrodes. The overall ratio between the amplitudes obtained with implanted electrodes and with needle electrodes was 1.4 for peak la and 2.5 for peak IV of the ABR. The exposure to rc-heptane (4000 p.p.m.) reduced the amplitudes of components la and IV of the ABR. The reduction was most consistent for component IV and most pronounced at higher frequencies and intensities. The reduction in ABR corresponds to an increase in the auditory threshold of approximately 10 dB at all frequencies. Neither the latencies nor the interpeak latencies of components la and IV were changed. No significant changes in ABR were observed in the group exposed to 800 p.p.m. The mechanism behind the ototoxicity of organic solvents is discussed.     

Mechanism of the enhancement in transmitter release from central and peripheral noradrenergic nerve terminals induced by the purified scorpion venom,tityustoxin

Summary In the isolated nerve-muscle preparation of the cat nictitating membrane exposure to 0.04 M of the scorpion venom tityustoxin (TsTX) increased significantly the overflow of ³H-noradrenaline and the responses elicited by postganglionic nerve stimulation (1200 pulses, 0.5 ms duration, supramaximal voltage). Concentration effect curves to exogenous (-)-noradrenaline were not affected in the presence of this concentration of TsTX.The enhanced release of ³H-noradrenaline obtained during nerve stimulation as well as the increase of the postsynaptic responses observed during exposure to TsTX were more pronounced at 4 Hz than at 20 Hz. The increase in the overflow of noradrenaline observed with the toxin was selective for nerve stimulation since the release evoked by tyramine was not affected by TsTX.TsTX did not increase further the enhancement of ³H-noradrenaline release obtained in the presence of 18 mM tetraethylammonium (TEA). On the other hand, both TsTX and TEA were able to increase further the overflow of ³H-noradrenaline after block of the presynaptic alpha-adrenoceptors with phenoxybenzamine 0.29 or 2.9 M.In slices of rat cerebral cortex, TsTX 0.04 M increased ³H-noradrenaline release induced by 10 mM and by 20 mM KCl. The increased release evoked by the toxin was more pronounced for the lower concentration of K⁺.An increased release of ³H-noradrenaline in the presence of the toxin was also observed in rat hypothalamic slices stimulated with 20 mM K⁺. The K⁺ stimulated induced release of ³H-noradrenaline was also increased by 1.8 mM TEA. As shown for the peripheral nervous, system the simultaneous addition of TEA and TsTX did not result in additive effects when compared with the effects of the two agents added separately. Tityustoxin did not modify the metabolic pattern of the neurotransmitter released by K⁺ from rat hypothalamic slices.It is concluded that TsTX increases the stimulation-induced release of ³H-noradrenaline from both peripheral and central noradrenergic nerve terminals. Tityustoxin appears to act on the nerve terminal by a mechanism similar to that of TEA, an agent known to enhance the amount of noradrenaline released by nerve stimulation by increasing the duration of the action potentials.     

Dose-dependent effects of vinyltoluene inhalation on non-protein thiols and drug biotransformation in liver and kidneys of the rat

1. Male Wistar rats were exposed to atmospheres of 50, 100 or 300 p.p.m. vinyltoluene 6h/day, 5 days/week, for one or two weeks.

2. Hepatic non-protein sulphydryl content decreased in a dose-dependent manner when measured 0·5?h after the last exposure, both after one and two weeks.

3. The content of hepatic non-protein sulphydryl groups progressively increased 20?h after stopping the vinyltoluene exposure.

4. The activity of 7-ethoxycoumarin O-deethylase showed a dose-dependent increase both in liver and kidneys. The activity of UDP-glucuronosyltransferase also increased in a dose-related manner in both organs studied.     

5-HT(2C) receptor activation is a common mechanism on proerectile effects of apomorphine, oxytocin and melanotan-II in rats

This study was conducted to determine the phosphorylation state of N-methyl-d-aspartate (NMDA) NR1 subunit on serine residues 896 (Ser896) and 897 (Ser897), the extracellular signal-regulated kinase 1/2 (ERK1/2), and the cyclic AMP response element-binding protein (CREB) after repeated exposure to cocaine (20 mg/kg, once daily for 9 days) in the dorsal striatum of rats. The real-time changes of glutamate concentration evoked by repeated cocaine injections were examined using a glutamate biosensor in order to evaluate the correlation between glutamate concentration and the change in these phosphoproteins. The results of this study showed that the immunoreactivity of phosphorylated (p)NMDA NR1 subunit at Ser896 and Ser897 as well as pERK1/2, but not pCREB, in the dorsal striatum was increased at 30 min and then returned to basal levels 4 h after repeated cocaine injections. Similarly, glutamate responses evoked by repeated cocaine injections were also increased 30 min after repeated cocaine injections for 3 days and were prolonged by the 9th day of treatment. However, the glutamate responses were not detected at 4 h after repeated cocaine injections for 5 days. In addition, the elevated immunoreactivity of the phosphoproteins 2 h after repeated cocaine injections was attenuated by the blockade of dopamine D1 receptors and NMDA receptors with the SCH23390 or MK801 antagonists, respectively. These findings suggest that glutamate release and dopamine D1 and NMDA receptor stimulation after repeated exposure to cocaine are associated with NMDA NR1 subunit, ERK1/2 and CREB phosphorylation in the dorsal striatum.     

The distribution,excretion and biotransformation of p-dichloro[14C]benzene in rats after repeated inhalation,oral and subcutaneous doses

1. Following repeated daily whole-body exposure (3h/day) of rats to atmospheres containing p-dichloro[¹⁴C]benzene (1000p.p.m.), or administration of oral or subcutaneous doses (250?mg/kg/day), 24-h tissue concn. of ¹⁴C were similar and did not increase after six days dosing, but tended to decrease.

2. After repeated daily atmospheric exposures or oral doses, highest concn. of ¹⁴C occurred in fat, kidneys, liver and lungs. Concn. declined rapidly to near or below limits of detection (< 0.2 p.p.m.) in plasma and tissues at 5 days. After similar subcutaneous doses, tissue concn. declined more slowly.

3. During five days after repeated dosing, most excreted ¹⁴C(91–97%) was in the urine. Little was excreted in faeces or expired air. Excretion was more prolonged following subcutaneous administration. After single doses to bile duct-cannulated animals, 46–63% of the excreted ¹⁴C was in the bile during 24h.

4. The pattern of metabolites in urine and bile was similar after each route of administration although there were quantitative differences. Urine extracts contained two major ¹⁴C-components, namely a sulphate and a glucuronide of 2,5-dichlorophenol, representing 46–54% and 31–34% of the urinary ¹⁴C respectively. Two minor components were identified by mass spectrometry as a dihydroxydichlorobenzene and a mercapturic acid of p-dichlorobenzene.

5. The glucuronide of 2,5-dichlorophenol was the major ¹⁴C component in bile (30–42%).     

Low level postnatal methylmercury exposure in vivo alters developmental forms of short-term synaptic plasticity in the visual cortex of rat

Methylmercury (MeHg) has been previously shown to affect neurotransmitter release. Short-term synaptic plasticity (STP) is primarily related to changes in the probability of neurotransmitter release. To determine if MeHg affects STP development, we examined STP forms in the visual cortex of rat following in vivo MeHg exposure. Neonatal rats received 0 (0.9% NaCl), 0.75 or 1.5 mg/kg/day MeHg subcutaneously for 15 or 30 days beginning on postnatal day 5, after which visual cortical slices were prepared for field potential recordings. In slices prepared from rats treated with vehicle, field excitatory postsynaptic potentials (fEPSPs) evoked by paired-pulse stimulation at 20–200 ms inter-stimulus intervals showed a depression (PPD) of the second fEPSP (fEPSP2). PPD was also seen in slices prepared from rats after 15 day treatment with 0.75 or 1.5 mg/kg/day MeHg. However, longer duration treatment (30 days) with either dose of MeHg resulted in paired-pulse facilitation (PPF) of fEPSP2 in the majority of slices examined. PPF remained observable in slices prepared from animals in which MeHg exposure had been terminated for 30 days after completion of the initial 30 day MeHg treatment, whereas slices from control animals still showed PPD. MeHg did not cause any frequency- or region-preferential effect on STP. Manipulations of [Ca²⁺]_e or application of the GABA_A receptor antagonist bicuculline could alter the strength and polarity of MeHg-induced changes in STP. Thus, these data suggest that low level postnatal MeHg exposure interferes with the developmental transformation of STP in the visual cortex, which is a long-lasting effect.