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Biomedical subjects

C V Vorhees

Publications and source records attributed to C V Vorhees.

At least 19 recordsLinked to original sources

Preliminary evidence for methamphetamine-induced behavioral and ocular effects in rat offspring following exposure during early organogenesis.

Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,l)-methamphetamine (MA) HCl (expressed as free base, N = 15) or distilled water (N = 6) by SC injection x 2/day in a 3 ml/kg volume on embryonic (E) days 7-12. Control rats were pair-fed to MA-exposed dams on days E7-18. No control dams failed to deliver; however, of 15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed litters). One additional MA litter had all the offspring die shortly after birth. There was no difference between groups on offspring postnatal (P) body weight. The offspring exposed prenatally to MA had significantly lower olfactory orientation scores (P9, 11, 13) to their home cage scent. In a test of early activity (P10, 12, 14) the MA-exposed progeny were marginally less active than controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened response latency on a test of acoustic startle (P27). Motor activity showed no differential response in MA treated or control offspring to MA (P63) or fluoxetine challenge (P70). However, the MA offspring were more active than controls with respect to central and side activity during the second week of testing. No group differences were found for performance in a straight swimming channel or on the number of errors committed or latency to escape in a complex (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny. However, MA did not effect hippocampal or neostriatal monoamine levels when measured on P28.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Psychotropic drugs as behavioral teratogens.

Three psychotropic drugs were administered to pregnant rats and were then evaluated for their behavioral and reproductive effects in the offspring. Control rats received either saline or vitamin A. Prochlorperazine had the most disruptive effects on reproduction and growth, but had the least effect on behavior. Propoxyphene had no apparent effects on reproduction or growth, but produced a variety of behavioral changes. Fenfluramine was intermediate in its effects on reproduction and growth and had behavioral effects that were revealed in tests of preweaning development. The data suggest that systematic tests of behavior add important information to evaluations of reproductive toxicity that cannot, at present, be obtained by other means.

Animals

Thiamin deficiency induced muricide behavior in rats.

An examination of the relationship between the degree of thiamin deficiency and the onset of deficiency induced muricide, revealed that this response appeared abruptly after 31 days of dietary treatment compared to pair-fed or ad lib fed controls. The response was not present after shorter periods of treatment (21 or 26 days). Moreover, once the response appeared at 31 days it was not increased significantly by additional thiamin depletion at 36 days (muricide rats of 48 and 61%, respectively). Pharmacologically induced thiamin deficiency using either pyrithiamin or oxythiamin also induced muricide (38% and 43%, respectively), albeit after a much shorter course of treatment. It appears that muricide induction is not related to thiamin deficiency induced encephalopathy and is probably a reflection of heightened irritability. Nevertheless, the induction of muricide was clearly not related to food deprivation and represents a useful pathognomonic sign that precedes the onset of neurological symptoms indicative of advanced thiamin deficiency.

Aggression

A comparison of methylphenidate induced active avoidance and water maze performance facilitation.

Methylphenidate was shown to facilitate both active avoidance and water performance compared to controls. Repetitive errors on both tasks were greater in the drug than the nondrug group and were positively correlated to water maze performance. These results fail to support the view that water maze acquisition is less influenced by performance variables than active avoidance. An unanticipated enhancement of water maze performance was also noted in the control group which had been previously tested on active avoidance compared with naive controls. Moreover, this group made fewer repetitive errors than naive controls, suggesting that previous shock exposure reduced inappropriate responses.

Animals

Facilitation of avoidance acquisition in rats produced by P-chlorophenylalanine or P-chloroamphetamine.

The effects of reducing brain serotonin using p-chlorophenylalanine (PCPA) were examined as a follow up to our previous report that reducing serotonin with p-chloroamphetamine (PCA) facilitated Y-maze avoidance acquisition and reduced open field activity. In the current work, PCPA was also found to facilitate Y-maze avoidance acquisition, while open field activity, although reduced, was not reduced significantly. In a second experiment, we re-examined PCA, except that the apparatus was changed in order to test the generality of the effect of PCA on avoidance performance in a task other than the Y-maze. Testing was also run at varying shock intensities to determine if this was a significant determinant of the effect. PCA reliably facilitated shuttle-box avoidance acquisition and did so at all shock intensities tested. Finally, in a third experiment, the time course of the onset of the PCA-induced avoidance facilitation was examined and found to develop 8--10 hours following drug treatment and not at a shorter drug to test interval of 4 hours. The present data, in conjunction with our previous data support the concept that lowered brain serotonin content facilitates avoidance acquisition regardless of the specific method used to reduce serotonin or to assess avoidance acquisition.

Amphetamines

A preliminary test battery for the investigation of the behavioral teratology of selected psychotropic drugs.

Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken. The test methods used in this study appear to be a reasonable initial approach to the development of neurobehavioral screening procedures which are comprehensive, sensitive, and usable.

Animals

Interlaboratory comparison of behavioral testing.

New requirements by several regulatory agencies for testing the psychotoxic potential of new drugs, chemicals, and environmental contaminants raise unique problems. In order to assess intra- and interlaboratory reliability of behavioral tests a model animal maze learning procedure was designed and run in 3 cooperating laboratories. Uniform procedures were written and identical mazes were constructed. Normal control animals of identical age and sex, but of different strains, were used by the participants. A positive control group of neurologically impaired rats was run by one laboratory. Significant differences in test results among the laboratories were found. Data obtained from the positive control animals (mean errors=28.3) indicated a learning impairment statistically significant compared to the negative control data (mean errors=12.7) from any of the participating laboratories. Based on the results of this study, a reasonable standard of interlaboratory reliability in behavioral testing appears an attainable goal.

Animals

The relationship of gestational age to vitamin A induced postnatal dysfunction.

In an effort to determine the relationship between time of administration and consequent behavioral effects on progeny, a uniform subteratogenic dose of vitamin A (80,000 I.U./KG) was administered to gravid Sprague-Dawley rats during one of five periods of gestation (days 5-7, 8-10, 11-13, 14-16 and 17-19). Offspring were examined for changes in rate of weight gain, locomotor activity and maze learning ability (T-maze with return to nest as reward and multiple T water maze escape). Vitamin A 8-10 animals were hyperactive, vitamin A 11-13 animals acquired T-maze slower than controls and both vitamin A 8-10 and 11-13 acquired water maze slower than controls. Vitamin A 11-13 animals were significnatly lighter than controls and all other vitamin A groups.

Animals

Induced PKU in rats: effects of age and melatonin treatment.

Newborn rats injected on Days 1-8 of life with L-phenylalanine (2 g/kg) and p-chlorophenylalanine (80 mg/kg) displayed biochemical symptoms analogous to human phenylketonuria (PKU) and maze learning impairments. The behavioral effects were less evident in rats treated on Days 9-16 or 7-24. None of the symptoms observed were alleviated by simultaneous administration of melatonin (10 mg/kg/day).

Aging

Effects of thiamin deficiency on acetylcholine levels and utilization in vivo in rat brain.

Cerebral regional acetylcholine (ACh) levels and utilization were studied in vivo in thiamin deficient (TD), pair-fed asymptomatic (PFC) and ad libitum fed control (ALC) rats. ACh levels in the cortex, corpus striatum, midbrain, diencephalon and brainstem of TD rats were comparable to those observed in the control groups. However, ACh utilization was slightly to moderately (10-41%) decreased in cortex, midbrain, diencephalon and brainstem. The decrease was significantly different in the midbrain of TD rats as compared to PFC and ALC rats.

Acetylcholine