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PubMedDate not supplied

Temporal changes in dopaminergic and serotonergic function caused by administration of trimethyltin to adult rats.

Previous studies have demonstrated that at day 7 following treatment, administration of 3 or 7 mg/kg trimethyltin (TMT) to male Long-Evans rats caused decreases in the concentrations of DA in nucleus accumbens, and perturbed serotonergic function in regions of brain that receive serotonergic innervation from the raphe nuclei. The present series of experiments extended these observations by examining the time course of these events from 14 to 28 days after treatment. Following a dose of 7 mg/kg, changes in serotonergic function, as evidenced by increased turnover and decreased concentrations of 5-HT, were present in striatum, olfactory tubercle, septum and frontal cortex. In nucleus accumbens, concentrations of DA were decreased up to 21 days, while in frontal cortex concentrations of DOPAC and HVA were elevated only at 14 days. In concert with our previous studies, these data indicate that administration of TMT continues to affect serotonergic systems up to 28 days, and dopaminergic systems up to 21 days after exposure, with striatum, nucleus accumbens, olfactory tubercle and septum exhibiting persistent effects due to administration of this neurotoxicant. These prolonged alterations in serotonergic function suggest that this system may play an important role in the response to intoxication with TMT.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Use of avidin-biotin subtractive hybridization to characterize mRNA common to neurons destroyed by the selective neurotoxicant trimethyltin.

Trimethyltin (TMT), a selective neurotoxicant, destroys a distinct subpopulation of neurons which possess no known biochemical or anatomic linkage. However, TMT-sensitive neurons may share common gene products related to susceptibility. In an effort to isolate mRNAs common to TMT-sensitive neurons, avidin/biotin based-subtractive hybridization was used to generate a cDNA library specifically related to TMT-toxicity. Out of 50 cDNAs, two clones hybridized only to poly(A+) mRNA isolated from the brains of saline-treated rats. Two of these cDNAs, p9T10 and p9T19, were used for in situ hybridization; both hybridized to hippocampus, limbic cortex, amygdala and other regions destroyed by TMT, suggesting that these probes identified mRNA enriched in TMT-sensitive neurons. The patterns of in situ hybridization coupled with the loss of p9T10 and p9T19 hybridization to mRNA isolated from the brains of TMT-treated rats suggests that one or both of these two clones may represent mRNA found in neurons damaged by TMT. The combination of selective neurotoxic lesions followed by cDNA subtractive hybridization should prove to be a useful strategy for the isolation of gene products from specific neuronal populations.

Animals↗

PubMed1984

The neurotoxicity of trimethyltin chloride in hamsters, gerbils and marmosets.

Trimethyltin chloride (TMT) was given to Syrian hamsters, gerbils and marmosets, and the changes in the brain were studied 1 day to 7 weeks later by light and electron microscopy. Within the marmoset brain, TMT was found to be uniformly distributed, similar to that in the rat. In all three species, signs of poisoning included whole-body tremors and prostration, while death might occur in 3-4 days; in marmosets ataxia, agitation, aggression and occasional fits were also observed. Bilateral symmetrical neuronal necrosis and chromatolysis were seen in the majority, which involved the hippocampus, pyriform cortex, amygdaloid nucleus, neocortex, various brain stem nuclei and in marmosets the retina. The probably lethal dose of TMT in all three species is approximately 3 mg kg-1, while the LD50 for the rat is 12.6 mg kg-1. The lower figure is probably related to lack of binding to haemoglobin in contrast to the binding in the rat. TMT does not bind to human haemoglobin and thus the predicted lethal dose for humans may be about 3 mg kg-1 (15.1 mumol kg-1), while the dose required to produce neuronal damage could well be less.

Animals↗

PubMed1987

Increased free intrasynaptosomal Ca2+ by neurotoxic organometals: distinctive mechanisms.

Effects of several alkylmetals on free intrasynaptosomal Ca2+ concentration, [Ca2+]i, were studied in vitro using the fluorescent Ca2+ indicator fura-2. Neurotoxic alkylmetals methylmercury (Met-Hg), triethyllead (TEL), triethyltin (TET), and trimethyltin (TMT) (at 2.5-30 microM) increased [Ca2+]i to different degrees. Met-Hg was the most potent, elevating [Ca2+]i 100-800 nM, dose dependently and significantly more than high K+ (150 nM) or veratridine (350 nM). The effect of Met-Hg could not be inhibited with a Ca2+ channel blocker, verapamil, nor with a Na+ channel blocker, tetrodotoxin. Inhibition of the mitochondrial Ca2+ uptake in situ with rotenone + oligomycin decreased the potency of Met-Hg to elevate [Ca2+]i but did not change the resting [Ca2+]i. Met-Hg also slightly decreased synaptosomal ATP. TEL and TET elevated [Ca2+]i by 100-200 nM. The effect of TEL, but not that of TET, could be blocked with verapamil (36%) and veratridine (67%). TEL was less efficient in the presence of ouabain. Neither TEL nor TET had significant mitochondrial effects in situ contributing to [Ca2+]i. TMT increased [Ca2+]i less than TET while dimethyltin and methyltin were inactive. These results indicate that neurotoxic derivatives of alkylmetals studied increase [Ca2+]i. This occurs mainly either by nonspecific increase (Met-Hg, TET) of Ca2+ leakage through the plasma membrane and/or specific interference with the mechanisms regulating Ca2+ fluxes through the plasma membrane (TEL).

Adenosine Triphosphate↗

PubMed1988

Behavioral and physiological effects of trimethyltin in the rat hippocampus.

An injection of trimethyltin (TMT) into adult male Wistar rats produced a transient hyperirritability and aggressive behavior. When these effects of the drug subsided, the rats were still markedly impaired in performance of a spatial memory task examined in a watermaze. Activity of neurons in the hippocampus of these TMT-treated rats was studied in a slice preparation. A large (8 mg/kg) or double (7.5 and 3.5 mg/kg, two weeks apart) i.p. injection of TMT caused a loss of slow inhibitory postsynaptic potentials recorded in CA1 neurons in response to stimulation of stratum radiatum. A loss of accommodating properties of the neurons in response to a prolonged depolarizing current pulse was also seen in some of these cells. Other resting properties of the neurons were within the normal range. Topical application of acetylcholine (ACh) produces in normal hippocampal neurons a depolarizing response and a blockade of after-hyperpolarization. Only the latter response to ACh was seen in cells from TMT treated rats. No effect of the drug on reactivity to serotonin was detected. These effects of TMT were not seen when the drug was applied acutely while recording from cells in the slice indicating that it involves a degeneration process. These results suggest that the cognitive deficits in TMT treated rats might be associated with deficits in cholinergic functions.

Acetylcholine↗

PubMedDate not supplied

The disposition of 14C-trimethyltin in the pregnant rat and fetus.

Trimethyltin (TMT) is a potent neurotoxicant. For unknown reasons, age at exposure to TMT may dramatically influence the severity of TMT-induced neuropathology. We have demonstrated previously that radiolabel derived from [14C]-TMT given to pregnant dams on gestational day (GD) 17 is found in fetal brain and blood. The present study was designed to determine the distribution of radiolabel derived from [14C]-TMT to brain and other tissue in fetuses from dams dosed on either GD 12 or 17 with 7.0 mg/kg TMT chloride. Radioactivity in GD 12 and GD 17 maternal whole blood peaked 1 hour after IP treatment. Whole blood elimination half-lives were 12-15 days. Peak radiolabel concentrations in GD 12 maternal and fetal brain were only 11-30% of those from GD 17 animals, however, peak fetal brain concentrations of radiolabel were not different from their respective maternal brain concentrations. Radiolabel concentrations in liver, kidney, and adrenal of GD 17 dams were higher than those in corresponding GD 12 tissues. Combined urinary and fecal elimination of radiolabel for two weeks after dosing accounted for 31 and 22% of the GD 12 and 17 doses, respectively. It appears that gestational age influences the distribution and elimination of TMT in the rat.

Aging↗

PubMed1991

Triorganotin inhibition of rat cardiac adenosine triphosphatases and catecholamine binding.

Triorganotins have been reported to affect heme metabolism as well as the cardiovascular system. Our recent studies indicated that these organotins inhibit cardiac sarcoplasmic reticulum Ca(2+)-transport and cAMP-stimulated phosphorylation of specific proteins involved in Ca2+ transport, suggesting their interference with cardiac adrenergic function. The present study determines the effect of three organotins--tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT)--on rat cardiac ATPases and catecholamine binding, since these phenomena are involved in cardiac function. Cardiac membrane fraction was prepared from heart ventricles of male Sprague-Dawley rats. All three organotins inhibited cardiac Na+,K(+)-ATPase, [3H]ouabain binding, K(+)-activated p-nitrophenyl phosphatase (K(+)-PNPPase) and oligomycin-sensitive (OS) and oligomycin-insensitive (OI) Mg(2+)-ATPase in a concentration-dependent manner. K(+)-PNPPase was less sensitive to these triorganotins when compared to Na+K(+)-ATPase, suggesting that triorganotins affect the Na(+)-pump activity by acting on the Na(+)-dependent phosphorylation process. OS Mg(2+)-ATPase was more sensitive to these organotins when compared to OI Mg(2+)-ATPase, confirming their potent effect on the enzymes of oxidative phosphorylation. The order of potency is TBT greater than TET greater than TMT. TET and TMT, but not TBT, inhibited [3H]norepinephrine and [3H]dopamine binding to cardiac membranes in a concentration-dependent manner, the effect being more with TET. These results suggest that triorganotins inhibit sodium pump activity as well as ATP synthesis. Since Na+,K(+)-ATPase is involved in the active transport of catecholamines, triorganotins not only inhibited the catecholamine transport but also to some extent affected catecholamine binding, thus interfering with cardiac function.

Adenosine Triphosphatases↗

PubMed1985

Effects of trimethyltin on homecage behavior of rats.

Diurnal patterns of feeding, drinking, locomotor activity, and rearing in male Fischer-344 rats were examined for 2 weeks after a single oral dose of trimethyltin chloride (TMT) at 0, 3, 5, or 7 mg/kg. Body weights and feeding and drinking efficiency ratios (ratios of amount of food or water consumed per unit effort) were also determined daily. TMT caused a dose- and time-related drop in body weight; two of five rats in the 7 mg/kg group were killed moribund on 15 days after dosing. Feed consumption fell to 25% of control within 5 days after 7 mg/kg TMT, and to 50% of control for Days 2 and 3 after 5 mg/kg TMT. Water consumption doubled within 2 days after 7 mg/kg TMT and remained elevated for 2 weeks. Feeding efficiency dropped to 40% of control after 7 mg/kg, but drinking efficiency was unchanged. The diurnal patterns of drinking and of rearing were disrupted at all doses of TMT; a normal peak in rearing activity, occurring immediately prior to light onset, was markedly attenuated after all doses on Day 3, and at 5 and 7 mg/kg on Days 5 and 7 post-TMT. These results suggest (1) that the regulation of feed and water intake is severely compromised after a high dose of TMT, and (2) that the rat's cyclical patterns of homecage behavior are sensitive to TMT doses as low as 3 mg/kg.

Animals↗

PubMed1990

Trimethyltin effects on auditory function and cochlear morphology.

Trimethyltin (TMT) is a neurotoxicant known to alter auditory function. The present study was designed to compare TMT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. Adult male Long-Evans hooded rats (n = 9-12/group) were acutely exposed to saline, 3, 5, or 7 mg/kg TMT. Auditory thresholds were determined 11 weeks postdosing for 5- and 40-kHz tones using reflex modification of the auditory startle response (ASR). Brainstem auditory evoked response (BAER) thresholds were determined for 5-, 40-, and 80-kHz tonal stimuli 9 weeks postdosing. Cochlear histology was assessed at 13 weeks postdosing. Functional endpoints demonstrated a high-frequency hearing loss. ASR thresholds for 40-kHz tones were elevated 25-35 dB in all dosage groups. BAER thresholds for 40- and 80-kHz tones were elevated 30-50 dB in the 5 and 7 mg/kg groups. Organ of Corti surface preparations revealed a pattern of damage suggesting classical ototoxicity. That is, outer hair cells died preferentially in regions associated with high-frequency hearing, in a dosage-dependent manner from base to apex. These data demonstrate the utility of the ASR and BAER in detecting functional alterations in audition and indicate that TMT-induced high-frequency hearing loss is associated with cochlear damage.

Animals↗

PubMed1981

Pathogenesis of trimethyltin neuronal toxicity. Ultrastructural and cytochemical observations.

The ultrastructural cytopathologic and cytochemical effects of trimethyltin (TMT) neurotoxicity were delineated in hippocampal and pyriform neurons of acutely intoxicated adult rats. TMT produced neuronal necrosis that preferentially involved hippocampal formation pyriform cortex. The first subcellular alterations were multifocal collection of dense-cored vesicles and tubules and membrane-delimited vacuoles in the cytoplasm of the perikaryon and proximal dendrite. Ultrastructural cytochemical examination revealed that the vesicles and tubules had acid phosphatase activity analagous to Golgi-associated endoplasmic reticulum (GERL). Shortly after the appearance of the GERL-like vesicles and tubules, autophagic vacuoles and polymorphic dense bodies accumulated in the neuronal cytoplasm. Some dense bodies appeared to arise from the dense-cored tubules. Neuronal necrosis was characterized by increased electron density of the cytoplasm and large, electron-dense intranuclear masses. Alterations of mitochondria and other organelles were not observed in the early stages of cell injury. No light- or electron-microscopic alterations were found in liver or kidney. Comparable subcellular alterations were observed in adult and neonatal rats chronically intoxicated with TMT. A series of other trialkyl and tricyclic tins and dimethyltin did not produce similar pathologic findings. The GERL-like accumulations are unique in neuronal cytopathology. These findings suggests that GERL and autophagy play an important role in the pathogenesis of TMT-induced neuronal injury.

Animals↗

PubMed1990

Neurochemical changes in hippocampal and caudate dialysates associated with early trimethyltin neurotoxicity in rats.

Following a control period of dialysis of the hippocampus (Hc) or caudate (Cd) of conscious freely-moving rats, a single dose of trimethyltin chloride (TMT, 10 mg/kg) was administered by gavage and dialysis continued for up to 51 hr after dosing. During this time dialysate levels of amino acids, catechols and indoles were continually monitored, GABA A and B and glutamate (Glu) binding was measured at 48 hr, and histological damage was assessed at 24, 48 and 72 hr after dosing. The earliest change to occur was a significant 2-fold increase at 24 hr in Hc and Cd dialysate levels of glutamine (Gln), followed at 48 hr by an almost 4-fold increase in Gln and increases also in Glu, GABA and threonine levels. 5-Hydroxyindoleacetic acid (5-HIAA) levels were also increased in Cd dialysates 24 and 48 hr after dosing. The initial increase in Gln occurred at a time (24 hr) when there was no necrosis, only mild cytoplasmic changes in the CA3b region of the Hc and none in the Cd. By 72 hr cytoplasmic and necrotic changes were well established in both Hc and Cd. GABA A binding was significantly decreased in both Hc and Cd 48 hr after dosing, while Glu binding was unchanged. The results suggest that one component of TMT-induced neurotoxicity may be a consequence of increased extracellular levels of the excitotoxic amino acid, glutamate.

Amino Acids↗

PubMed1986

Increased synthesis of membrane macromolecules is an early response of retinal neurons to trimethyltin intoxication.

We studied the synthesis and axonal transport of proteins and glycoproteins in the visual system of adult Long-Evans rats that had received 4 weekly doses of trimethyltin hydroxide (TMT, 4 mg/kg b. wt.) by gastric intubation. One week following the last dose, an in vitro assay was used to study the rate of incorporation of radioactive precursors into various macromolecules of isolated retinas. Retinas from TMT-treated rats showed increased apparent rates of synthesis, relative to retinas from control rats, for proteins [( 35S]methionine precursor) and glycoproteins [( 3H]fucose precursor). Gel electrophoretic analysis of newly synthesized proteins indicated that the increased synthesis was a generalized effect, i.e. it was not restricted to a select subset of proteins. The axonal transport of these macromolecules by retinal ganglion cells to axons (optic tract) and nerve endings (superior colliculus) was examined in vivo following intraocular precursor injection. The amount of material transported, relative to that synthesized in the retina, was not appreciably altered in TMT-treated rats, indicating that TMT did not selectively impair axonal transport. The biochemical changes were accompanied by minimal ultrastructural alterations and little neuronal necrosis in the retina. We suggest that TMT induces increased synthesis of membrane macromolecules in retinal neurons; this may reflect an early reactive (compensatory) response rather than a regressive (degenerative) response of retinal neurons to TMT. Our data do not support the hypothesis that TMT induces a functional impairment of neuronal endoplasmic reticulum or Golgi apparatus.

Animals↗

PubMedDate not supplied

Effects of trialkyltins on the schedule-controlled behavior of the pigeon.

Male White Carneaux pigeons trained to respond for food under a multiple fixed-ratio fixed-interval schedule of reinforcement were given single injections of trimethyltin (TMT), or triethyltin (TET). A dose of 0.3 mg/kg TMT produced no effect on behavior, while a 1.0 mg/kg dose was a threshold dose and 1.75 mg/kg produced behavioral changes that persisted for months in some birds. TMT produced effects on responding under the multiple schedule at approximately the same doses that produce neuronal damage in the hippocampus and the brain stem of the pigeon. Higher doses given to untrained birds produced signs of extensive neurological damage. A dose of 1.0 mg/kg of TET decreased rates of responding under both schedule components three hours after administration, but behavior usually had recovered by the next day. Doses of 3.0 and 5.6 mg/kg had similar effects, but responding did not recover for several days. Some birds showed significant rate increases, especially under the fixed-interval component several days to several weeks after TET administration. Doses greater than 10 mg/kg TET were lethal. Dose-effect curves for the effects of d-amphetamine, chlorpromazine and morphine on responding under the multiple schedule were determined for some birds before and one month after 1.0 and 1.5 mg/kg of TMT. TMT shifted the dose-effect curve for d-amphetamine to the right, but it did not produce systematic changes in the dose-effect curves for morphine and chlorpromazine.

Animals↗

PubMedDate not supplied

Imparied maze performance in the rat caused by trimethyltin treatment: problem-solving deficits and perseveration.

Trimethyltin (TMT) produces cytological damage to several limbic-forebrain structures which is accompanied by behavioral changes including hyperactivity and aggressiveness. The purpose of this investigation was to determine whether the problem-solving capacity of the rat is affected by TMT treatment. Either 7.0 mg/kg of TMT ([CH3]3SnCl) or 0.9% saline was injected by gavage into the gastric lumen of each rat. The treated and non-treated animals were divided into two groups of nine each and tested subsequently on a series of Hebb-Williams maze problems. In comparison to the controls, the tin-treated rats made markedly more errors on all but one of the maze patterns. Moreover, the rate of error reduction across problems over the 10 daily trials was significantly retarded in the lesioned animals. In addition to these severe problem-solving deficits, the TMT-treated rat often exhibited a characteristic pattern of perseverative behavior while running in the maze. The pattern was not unlike stereotypies associated with the psychomotor pathology observed following treatment with certain drugs. Overall, the results of the performance of the animal in the Hebb-Williams task provides a corollary with the child afflicted with minimal brain dysfunction (MBD) and, thus, a model for MBD is suggested.

Animals↗

PubMedDate not supplied

A time-course study of trimethyltin induced neuropathology in rats.

The extent and time course of trimethyltin (TMT) induced lesions in the rat nervous system was studied. Adult Long-Evans rats were treated with a single dose of 6.0 mg TMT/kg b.w. and were sacrificed at 8 hours, 3, 15, 30 or 60 days following exposure. Histopathological examination of the brains revealed that neurons in the pyriform/entorhinal cortices and in the olfactory tubercle were extremely sensitive to TMT toxicity showing significant necrotic changes 3 days after exposure. Extensive neuronal loss and astrogliosis were observed 15 days after intoxication. In the hippocampal formation, the granule cells of fascia dentata showed early changes; however, evidence of toxic destruction in this area was not extensive and subsided considerably by the 3rd week of intoxication. On the other hand, destruction of the pyramidal neurons in Ammon's horn became more pronounced throughout the experimental period, resulting in extensive cell loss in this structure. It is interesting to note that the CA3 neurons in the anteromedial (septal) portion of the Ammon's horn appeared to be more vulnerable than those located more laterally (temporally), while the reverse pattern was observed for the CA1,2 neurons. Large mesencephalic trigeminal neurons in the brain stem also showed early chromatolytic changes. Since total normal morphology of these neurons was observed at later posttreatment time without apparent neuronal loss in these areas, total recovery of these nerve cells could be postulated.

Animals↗

PubMed1985

The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement.

Rats were trained to respond under a schedule of reinforcement in which only those responses separated by a 10-to 14-sec period of no responding produced a feed pellet (DRL 10 to 14 sec). Each rat received a single dose of trimethyltin (TMT) (5.6, 7.5, or 10 mg/kg) or triethyltin (TET) 1, 3, 4.25, or 5.6 mg/kg). The lowest dose of TMT (5.6 mg/kg) and the lowest dose of TET (1 mg/kg) were without significant effect. At 7.5 mg/kg and 10 mg/kg TMT, the percentage of the total responses spaced 10 to 14 sec apart decreased over the first 8 to 12 days after TMT. Those rats receiving 7.5 mg/kg TMT gradually returned to control values over the next 2 to 3 weeks while those rats receiving 10 mg/kg never recovered. Rats receiving 3, 4.25, and 5.6 mg/kg TET showed a decrease in the percentage of reinforced responses immediately after receiving TET. The behavior of those rats receiving 3 mg/kg returned to control values in 24 hr. Following 4.25 mg/kg TET, the health of the rats deteriorated rapidly. They were kept alive through heroic measures, but then were killed after testing on the 12th day following TET due to their failing health. At 5.6 mg/kg, the rats were killed on the 4th day due to failing health. These results indicate that TMT and TET differ with respect to potency and time course. The behavioral deficits produced by TET parallel the time course of general toxicity while the behavioral effects of acute TMT administration can persist in time long after the general appearance of the rats has returned to normal.

Animals↗

PubMed1984

Biochemical, functional and morphological indicators of neurotoxicity: effects of acute administration of trimethyltin to the developing rat.

The neurotoxic organometal, trimethyltin (TMT), was administered to rats on postnatal day (PND)5. Neurotoxicity was assessed throughout subsequent development using morphological, biochemical and functional endpoints. These consisted of brain weight measures and histology (morphology), assays of nervous system-specific proteins (biochemistry) and neurobehavioral indices of activity and learning (function). All three indices were affected. TMT caused dose-related decreases in brain weights at all ages examined, PND13, 22 and 66, with the hippocampus being the most severely reduced. Histological examination of the hippocampus revealed loss of pyramidal neurons in CA3 to CA4. Exposure to TMT was followed by dose- and age-dependent reductions in synapsin I, a neuron-specific phosphoprotein associated with synaptic vesicles; these effects of TMT were greater in hippocampus than in forebrain. TMT did not alter the concentration or protein composition of isolated myelin. The ontogeny of locomotion was altered in a dose- and time-dependent manner; TMT induced hypoactivity early in development (PND13) and hyperactivity by weaning (PND21); hyperactivity was also observed in the adult. Finally, TMT also affected learning ability throughout development. Deficits were observed in: acquisition and retention of an instrumental alleyway response; acquisition of a step-through passive avoidance response; and radial-arm maze performance. These results demonstrate the use of a multi-endpoint, multi-timepoint strategy for the detection and characterization of neurotoxicity.

Animals↗

PubMedDate not supplied

Behavioral toxicology of acute trimethyltin exposure in the mouse.

Adult BALB/c mice were injected IP with trimethyltin . HCl (TMT), and the effects of TMT were studied on gross behavior, lethality, spontaneous motor activity (SMA), and responding under a multiple fixed-ratio 30, fixed-interval 600 sec (mult FR30 FI600) schedule of reinforcement. Following doses of 4, 5, and 6 mg/kg, the cumulative 48-hr lethality was 10% at 4 mg/kg, IP, and 100% at 5 and 6 mg/kg, IP. No deaths were observed during the first 48 hrs following 3 mg/kg TMT. This non-lethal dose produced whole body tremors. The SMA of mice receiving 3 mg/kg was reduced to 70% during the first 24-hr period following TMT and some recovery of total activity was observed during the second 24-hr period. The reduction in SMA was accompanied by a change in the normal circadian cycle of activity. Responding under the mult FR30 FI600 schedule was severely disrupted. Three hours after TMT administration and rate of responding in both components was decreased and the decrease became progressively larger over the next 48 hrs. In addition to the rate of FI600 responding being reduced, the normal pattern of FI responding was altered with an increase in responding observed in the early portions of the FI. These results suggest that the mouse is much more sensitive to the effects of TMT than the rat and may have potential as an animal model in the study of the neurotoxicity of TMT.

Animals↗