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D B Peele

Publications and source records attributed to D B Peele.

At least 19 recordsLinked to original sources
PubMed1995

Assessment of offspring development and behavior following gestational exposure to inhaled methanol in the rat.

The prospect of widespread human exposure associated with its use as an alternative fuel has sparked concern about the toxic potential of inhaled methanol (MeOH). Previous studies have revealed congenital malformations in rats following inhaled MeOH (Nelson et al. (1985). Fundam. Appl. Toxicol. 5, 727-736) but these studies did not include postnatal behavioral assessment. In the present study, pregnant Long-Evans rats were placed in exposure chambers containing 15,000 ppm MeOH or air for 7 hr/day on Gestational Days (GD) 7-19. The total alveolar dose of methanol was estimated at about 6.1 g/kg/day, for a total dose of about 42.7 g/kg for the entire study. Maternal body weights were recorded daily and blood methanol concentrations were determined at the end of exposure on GD 7, 10, 14, and 18. Following birth (Postnatal Day 0 [PND 0]), a number of tests were performed at various points in development, including: offspring mortality and body wt (PND 1,3), motor activity (PND 13-21, 30, 60), olfactory learning (PND 18), behavioral thermoregulation (PND 20-21), T-maze learning (PND 23-24), acoustic startle response (PND 24, 60), reflex modification audiometry (PND 60), pubertal landmarks (PND 31-56), passive avoidance (PND 72), and visual-evoked potentials (PND 160). Maternal blood MeOH levels, measured from samples taken within 15 min after removal from the exposure chamber, declined from about 3.8 mg/ml on the first day of exposure to 3.1 mg/ml on the 12th day of exposure. MeOH transiently reduced maternal body wt (4-7%) on GD 8-10, and offspring BW (5%) on PND 1. No other test revealed significant effects of MeOH. Prenatal exposure to high levels of inhaled MeOH appears to have little effect on this broad battery of tests beyond PND 1 in the rat.

Administration, Inhalation↗
PubMed1992

Functional dissociation of acute and persistent cognitive deficits accompanying amygdala-kindled seizures.

The effects of amygdala-kindled seizures on cognitive function were examined using long-delay flavor-aversion and passive-avoidance conditioning paradigms in rats. Experiments were conducted to compare the functional consequences of unilateral and bilateral kindled seizures (transient deficits) with those due to a kindling history only (persistent deficits). Animals with a history of unilateral or bilateral kindling demonstrated flavor-aversion conditioning that varied inversely with the delay separating saccharin (CS) and lithium (US). Unilateral stimulation during the CS-US interval produced an attenuation of flavor-aversion conditioning that was independent of delay value; bilateral stimulation eliminated conditioning all together. The effects of kindling and kindled seizures on passive-avoidance conditioning were functionally identical. Animals with a history of unilateral kindling demonstrated strong evidence of conditioning with no effect of posttraining seizures. In contrast, animals with a history of bilateral kindling were impaired in a passive-avoidance task. The impairment was evident in the presence or absence of seizure induction during training. Electrographic and behavioral indices of epileptiform activity produced by unilateral and bilateral stimulation failed to reveal any differences in seizure duration or severity. The results support the conclusion that cognitive disruption by amygdala-kindled seizures is task-dependent, does not show a temporal dependence, and cannot be explained on the basis of electrographic or behavioral measures of seizure severity alone.

Amygdala↗
PubMed1992

Olfactory toxicity of beta,beta'-iminodipropionitrile in the rat.

Following a pilot study which revealed olfactory epithelial degeneration induced by beta,beta'-iminodipropionitrile (IDPN), dose-response and time-course analyses were undertaken to further characterize the effects of IDPN on the olfactory system. Male rats were sacrificed at multiple time points ranging from 24 hr after a single dose to 56 days after three consecutive daily doses of IDPN (0-400 mg/kg i.p.). Nasal cavities were fixed, decalcified and embedded in paraffin; 5 microns sections were stained with hematoxylin and eosin, middle neurofilament protein antibody or olfactory marker protein antiserum. Olfactory bulbs were removed for slot blot analyses of glial fibrillary acidic protein, synapsin I and p38. Another group of rats was treated with saline or IDPN and perfused 6 hr or 1, 2, 3, 7, 14 or 28 days after the last dose. Olfactory bulb axonal degeneration was visualized using a modified Gallyas technique. Twenty-four hours after treatment with 200 or 400 mg/kg IDPN, there was severe, highly site-specific mucosal degeneration in the dorsal-medial nasal cavity; regeneration was incomplete 8 weeks later. IDPN increased olfactory bulb glial fibrillary acidic protein, peaking 7 days after three daily 400 mg/kg doses, and remaining significantly elevated 8 weeks after treatment. Olfactory bulbs contained substantial silver deposition in afferent axon bundles in the glomerular layer, beginning 24 hr after the first dose and persisting for 14 days after dosing. Although only a portion of the olfactory epithelium was damaged by IDPN, all axon bundles entering the olfactory bulb were involved, suggesting the lack of a clear topographic arrangement of sensory endings in the olfactory bulb.

Animals↗
PubMed1991

Functional deficits produced by 3-methylindole-induced olfactory mucosal damage revealed by a simple olfactory learning task.

Methods for assessing functional consequences of olfactory mucosal damage were examined in rats exposed to 3-methylindole (3-MI). Treatment with 3-MI (400 mg/kg) induced severe degeneration of olfactory sensory epithelium followed by regeneration, fibrous adhesions, and osseous remodeling of the nasal passages. At 100 mg/kg, there was mild Bowman's gland hypertrophy while the sensory epithelium remained intact. Rats receiving 3-MI demonstrated a treatment-related deficit in acquiring an olfactory learning task which was not due to altered cognitive abilities, as determined by subsequent testing in a step-through passive avoidance task. The results confirm the conclusion that alterations in functional indices resulted from 3-MI-induced anosmia and demonstrate the utility of simple learning tasks in assessing functional capacity following olfactory epithelial damage in rats.

Animals↗
PubMed1990

Learning and memory deficits in rats following exposure to 3,3'-iminodipropionitrile.

Rats were examined using a learning and memory test battery 4 weeks following exposure to 3,3'-iminodipropionitrile (IDPN). Initial testing revealed deficits in olfactory discrimination and passive avoidance (PA) conditioning. In order to dissociate learning and performance effects, additional tests were conducted. First, to rule out the possibility that IDPN reduced the aversiveness of foot shock, rats were tested in a simple shock sensitivity paradigm. The results indicated no change in shock sensitivity produced by IDPN. Second, to determine if the hyperactivity produced by IDPN was responsible for deficits in conditioning, several additional tests were conducted including (a) repeated-trials active avoidance (AA) and PA conditioning, (b) a PA study which included both a 1- and 24-hr training-testing interval, and (c) long-delay flavor-aversion conditioning. Rats treated with IDPN required more conditioning trials to reach criterion on both AA and PA procedures suggesting that they were capable of performing the required response but acquired those responses at a much slower rate. The deficits in PA conditioning were similar at both the 1- and 24-hr training-testing interval. Finally, the effects of IDPN on flavor-aversion conditioning depended on the delay separating flavor intake and lithium administration during conditioning. Rats treated with IDPN demonstrated robust flavor aversions when trained with a 30-min but not with a 6-hr delay. In summary, the neurotoxic profile of effects produced by IDPN must be expanded to include a prominent cognitive component characterized by protracted deficits in learning and memory capacity. The present experiment illustrates how chemically induced disruption of learning and memory produced by IDPN can be experimentally dissociated from associate neurological symptoms using a simple, routine battery of neurobehavioral tests.

Animals↗
PubMed1989

Time-dependent deficits in delay conditioning produced by trimethyltin.

Trimethyltin (TMT) produces behavioral and cognitive deficits resulting, in part, from limbic system toxicity. To determine whether these effects result from learning deficits or accelerated memory loss, the present experiment examined two delay conditioning paradigms in rats previously treated with either saline or TMT. Saline-treated Long-Evans rats receiving injections of lithium after consuming saccharin-flavored water later avoided saccharin ingestion: the degree of avoidance varied inversely with the time (0.5, 3 or 6 h) separating initial saccharin availability and lithium injection. Rats treated with TMT (8 mg/kg IV, 30 days prior) showed impaired conditioning at the long but not the short or intermediate delay conditions, suggesting that the deficits were mnemonic and not associative. Similar delay-dependent deficits in rats treated with TMT were observed in a passive avoidance task that arranged one of two delays between response emission and shock delivery during training. The effects of TMT on delay conditioning were accompanied by reduced bodyweight and hippocampal pathology. In summary, TMT appears to alter the temporally dependent association of events (entering darkened compartment versus saccharin consumption) and consequences (foot shock versus lithium administration) during acquisition. Furthermore, the observed deficits in delay conditioning produced by TMT did not appear to be task specific, with similar effects determined with tests of both somatosensory and gustatory avoidance learning designed to distinguish between functional alterations due to deficits in memorial processes from those due to altered sensory, motor, or associative processes.

Animals↗
PubMed1989

Strategies for assessing learning and memory, 1978-1987: a comparison of behavioral toxicology, psychopharmacology, and neurobiology.

Tests of learning and memory are currently not typically included in first-tier screening batteries even though there is ample evidence that chemical exposure can produce deficits in these cognitive processes. The approach taken in behavioral toxicology has been to restrict these cognitive tests to second tier or hazard characterization studies, yet there is little agreement on which tests are most appropriate. The present survey was designed to determine the current testing strategies in toxicology for detecting and characterizing the effects of chemical treatment on learning and memory, and to make comparisons to similar data from the fields of psychopharmacology and neurobiology. The survey data revealed a number of discipline-dependent effects on the selection of tests. A number of these effects were clearly related to the subject matter as well as the particular chemical/treatment being examined. Given the youth of the field, behavioral toxicology has the advantage of gaining valuable information from both of these disciplines. Behavioral testing in neurotoxicology should consider strategies which maximize unification of these closely related fields of neuroscience.

Animals↗
PubMed1988

Effects of selection delays on radial maze performance: acquisition and effects of scopolamine.

The effects of post-selection confinement (delays) on both the acquisition of performance and the response to the muscarinic blocker, scopolamine, were examined in an automated version of the eight arm radial maze. Long-Evans rats, exposed to post-selection delays of 0.5 sec (n = 4) or 100 sec (n = 4) during daily training trials did not differ in either the number of trials to acquire an accurate baseline of performance or in the amount of time required to obtain all eight food pellets. However, the pattern (delta-arm scores) of within-session arm selections demonstrated by the two groups of rats differed. Rats exposed to the 0.5-sec delay typically selected arms adjacent to arms from which they exited while rats exposed to the 100-sec delay were more likely to enter arms 2-removed from the exit arm. When scopolamine (0.03 to 1.0 mg/kg) was administered prior to testing, rats in the 100-sec delay group showed a greater reduction of accuracy and a larger increase in selection latency than rats in the 0.5-sec delay group. The differential effect of delay value on delta-arm scores was also eliminated in a dosage dependent manner with scopolamine. Scopolamine methylbromide (0.3 mg/kg) was found to have little effect on performance. In summary, the results indicate that the post-selection delay procedure is a sensitive and selective test for chemical-induced dysfunctioning of spatial memory in rats.

Animals↗
PubMed1988

Behavioral consequences of chelator administration in acute cadmium toxicity.

The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received ip administration of cadmium either alone or in combination with sc administration of BAL or DMSA. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete attenuations of conditioned flavor aversions when compared to the flavor aversions of rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hr. Attenuation of cadmium-induced aversions by BAL and DMSA extends earlier findings of an attenuation of lead-induced flavor-aversion conditioning by these complexing agents, and thus demonstrates further the utility of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions.

Animals↗
PubMed1988

Effects of scopolamine on repeated acquisition of radial-arm maze performance by rats.

Rats repeatedly acquired the performance of selecting only the four baited arms in an automated eight-arm radial maze, with the arms containing food pellets randomly assigned prior to each session. During each 14-trial (trial: obtain all four pellets) daily session, the number of errors (selecting nonbaited arms or repeating arm selections) showed a within-session decline, and choice accuracy for the first four arm selections showed a positive acceleration across trials for all rats. An index-of-curvature statistic, calculated for total errors, was used to quantify both the within- and between-session improvement of performance. Scopolamine (0.03 to 0.3 mg/kg, ip), but not methylscopolamine (0.3 mg/kg), reduced the accuracy of the first four selections of each trial and increased total within-session errors for all rats. Session times also were increased by scopolamine. An examination of within-session accuracy showed only slight signs of improvement at the higher dosages of scopolamine. The results indicate that behavior in transition states maintained by reinforcement contingencies in the radial maze is similar to that maintained by extended chained schedules, despite the fact that some of the stimuli controlling behavior in the maze are absent at the moment behavior is emitted.

Animals↗
PubMed1987

Conditioned flavor aversions: applications in assessing the efficacy of chelators in the treatment of heavy-metal intoxication.

A series of studies investigated the conditioned flavor aversions induced by administration of either lead or thallium in combination with either dimercaprol or dimercaptosuccinic acid in an attempt to correlate changes in flavor-aversion conditioning to changes known to alter the toxicity of metal administration. Rats received po administration of either thallium sulfate or lead acetate given alone or in combination with either dimercaprol or dimercaptosuccinic acid after consuming saccharin. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving either lead or thallium showed significant reductions in saccharin preferences (i.e., conditioned flavor aversions). Rats receiving lead acetate in combination with either of the two chelators displayed significantly reduced conditioned flavor aversions when compared to the aversions induced in rats receiving lead alone. Under the same conditions, there were no differences in the conditioned flavor aversions of rats receiving thallium only and those of rats receiving thallium in combination with either of the two chelators. Attenuation of the lead-induced conditioned flavor aversions was eliminated when chelator administration was delayed by 4 hr. This attenuation of lead-induced but not thallium-induced aversions by dimercaprol and dimercaptosuccinic acid demonstrates the sensitivity and selectivity of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions and is in agreement with clinical reports of effective chelation therapy in cases of lead but not thallium intoxication.

Analysis of Variance↗
PubMed1982

Autoshaped key pecking maintained by access to a social space.

When four experimentally naive pigeons were exposed to occasional forward pairings of a keylight followed by a doorlight (that signaled access to a large social space), all subjects began to peck the lit key. In a second experiment, where the keylight either preceded the presentation of the doorlight or was presented independently of it, key pecking was maintained only in the former circumstance. The unconditioned stimulus in these experiments--arrival in the social space--did not elicit pecking. Hence, the conditioned response of key pecking and the unconditioned response of entering the social space differed. This demonstration of autoshaping with a social-space unconditioned stimulus argues against a stimulus-substitution account of the findings.

Animals↗
PubMed1980

The contribution of an added counter to a fixed-ratio schedule.

Although previous research showed that a visual counter increased the rate of responding on a large fixed-ratio schedule, a theoretical analysis of the factors responsible for fixed-ratio performance suggests that the primary control by number of responses since reinforcement is to weaken the performance. The present experiment employed a multiple schedule in which the same fixed-ratio value alternated with and without an added counter. It tested the hypothesis that the differential reinforcement of high-rate responding masked the attenuation of the fixed-ratio performance from the unoptimal discriminative control produced by the fixed relation between number of responses and reinforcement. In the present experiment the postreinforcement pause was consistently longer in the components with the added counter, while running rates remained comparable between the components of the multiple schedule. Both components of the multiple schedule involved differential reinforcement of high-rate responding while only the components with the added counter amplified the discriminative control by number of pecks since reinforcement.

Journal Article↗
PubMedDate not supplied

Pyrethroid effects on schedule-controlled behavior: time and dosage relationships.

Pyrethroid insecticides have been divided into Types I and II based on behavioral profiles of toxicity produced by life-threatening dosages. In order to assess potential alterations in acquired (operant) behavior, acute dosage-effect and time-course determinations for permethrin (Type I) and cypermethrin (Type II) were made. Long-Evans rats responded for food according to a multiple schedule consisting of four different variable-interval schedules. Permethrin (100-400 mg/kg) and cypermethrin (7.5-60 mg/kg) were administered PO 1.5 hr pre-session and their effects on response rates and between-component response patterning determined. Permethrin reduced responding in a manner which was independent of the baseline response rate, while the rate reductions following cypermethrin administration showed a dependence on the baseline levels of responding, with low response rates showing differential sensitivity to disruption. When select dosages of each compound were delivered at various pre-session times, onset of and recovery from the rate-decreasing effects were more rapid with cypermethrin, with rates returning to baseline levels by 12 hr post-dosing. Responding was maximally suppressed 24 hr after administration of permethrin and returned to baseline levels 48 hr after administration. The disruption of response patterning following cypermethrin was maximal at 1.5 hr after administration, with complete recovery 12 hr post-dosing. Differential effects on response patterning, in potency, and in the time-course of effects of permethrin and cypermethrin suggest a type-specificity for pyrethroid effects on schedule-controlled behavior at dosages far below those producing lethality in rats.

Animals↗
PubMedDate not supplied

Conditioned flavor aversion induced by inhaled p-xylene in rats.

Xylenes have the potential for widespread public exposure, yet their neurotoxic properties are poorly understood. The conditioned flavor aversion (CFA) paradigm provides a sensitive behavioral assay for the aversiveness of many drugs and toxic chemicals. Male Long-Evans rats were placed on a restricted water schedule (30 min/day) 1 week after arrival in the laboratory at 40 days of age. Ten days later, all rats received 0.1% saccharin in place of water, and then were exposed immediately either to filtered air or to 50, 100, 200, 400, 800 or 1,600 ppm p-xylene for 4 hr, or to air or 400 ppm p-xylene for 0.5, 1, 2, 4 or 8 hr. The restricted water schedule remained in effect for the next 72 hr, at which time the rats were given a choice between saccharin and water. Inhalation of all concentrations of p-xylene reduced relative saccharin intake, with maximal aversion at 800 and 1,600 ppm. The aversion produced by 400 ppm p-xylene was maximal at exposures of 2 or more hr, with shorter exposures producing intermediate effects. Total fluid intake was unaffected by p-xylene exposure with the exception of a slight (nonsignificant) decrease in consumption following 1,600 ppm. Exposure to saccharin 24 hr prior to p-xylene produce no aversion, indicating that the reduction in saccharin intake required close temporal pairing of saccharin and p-xylene. Thus inhaled p-xylene at a concentration of 1/2 its TLV (= 100 ppm) caused a significant, learned change in rats' normal consumption of saccharin-flavored water, without disrupting total fluid consumption.

Administration, Inhalation↗
PubMedDate not supplied

Developmental neurotoxicity following neonatal exposure to 3,3'-iminodipropionitrile in the rat.

Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN), induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backward locomotion, and sensory disruption. We report here the behavioral effects of developmental exposure to IDPN in the rat. Animals were exposed (IP) to either saline, 75, 150, or 300 mg/kg/day on postnatal days (PND) 5-7. Animals were tested for: Figure-8 maze activity (PND 13-60); olfactory discrimination learning (PND 18 & 24); T-maze alternation and position discrimination learning (PND 25 & 26); acoustic startle response (PND 23, 61, & 62); passive avoidance (PND 70). To better define the dose response, a separate group of animals was exposed to either saline or 225 mg/kg/day (PND 5-7) and tested in the activity, T-maze, and startle paradigms. Animals exposed to 225 mg/kg/day and 300 mg/kg/day had decreased weight gain and lethality was 25% in the latter group. Signs of the IDPN syndrome, evident in the 225 and 300 mg/kg/day groups, persisted throughout the course of the study. IDPN exposed animals (300 mg/kg/day) were hyperactive on PND 17-60, failing to develop habituation in the Figure-eight maze until PND 60. The acoustic startle response was depressed for the 225 and 300 mg/kg/day groups on PND 23 only. Auditory thresholds were elevated for a high-frequency (40 kHz) but not a low-frequency tone (5 kHz) for the 225 and 300 mg/kg/day groups, indicating a hearing loss. IDPN treatment also disrupted performance of olfactory discrimination learning and produced cognitive deficits in T-maze learning in infants (300 mg/kg/day). That cognitive deficits also appeared in adulthood (PND 70) was demonstrated by learning deficits in a passive avoidance task at 150 and 300 mg/kg/day. IDPN (300 mg/kg/day) also caused a decrease in the wet weight of the whole brain (8%) and the cerebellum (12%) but not the hippocampus. These data demonstrate that short-term, neonatal exposure to IDPN in the rat produced persistent alterations in sensory, motor, and cognitive aspects of nervous system function.

Animals↗