Joan Havlena

Postnatal behavioral effects of tranquilizers administered to the gravid rat.

Abstract Gravid albino rats received reserpine, chlorpromazine, meprobamate, or a control injection of distilled water subcutaneously during one trimester of gestation on days 5–8, 11–14, or 17–20. A random sample of the surviving offspring selected at weaning was evaluated on measures of activity, emotionality, and audiogenic seizure susceptibility. Administration of transquilizers to the gravid animal resulted in alterations of behavior that persisted through adulthood. Evaluation of activity level on the inclined plane test at 25 days of age showed that the offspring of all of the drug-treated mothers were less active than control offspring. A similar decrease in activity and emotionality, as measured by responses on the open field test, was further observed when the animals were 55 days of age. Audiogenic seizure susceptibility, tested at 120 days of age, showed that the drug-group offspring were more resistant to audiogenic seizure stimuli than the control offspring. On all of these measures, no differences were found as a function of the trimester of gestation in which the drugs were administered. It was concluded that behavioral effects do result from the administration of tranquilizing drugs to the gravid animal, and that the behavioral changes induced are independent of the trimester of gestation and pharmacological differences between the drugs.

AUDIOGENIC SEIZURES IN ADULT MALE CASTRATED RATS TREATED WITH VARIOUS HORMONES.

Abstract Adult male albino rats of the Sprague-Dawley strain were castrated or shamoperated and evaluated for their susceptibility to audiogenic seizures at periodic intervals after surgery. These animals were maintained on daily administration of various hormones (testosterone, progesterone, or estradiol) at different dosage levels. A total of 378 animals, divided into 26 different groups according to their initial seizure susceptibility and treatment condition, were used. The results demonstrated that for the seizure-resistant animals, castration alone, or combined with testosterone or progesterone, did not significantly alter the incidence of audiogenic seizures. Estradiol significantly increased seizure incidence in the castrated groups. For the seizure-susceptible animals (castrated and sham-operated), both testosterone and progesterone caused a significant decrease in seizure incidence, whereas estradiol maintained the high level of seizure incidence.

EFFECTS OF PRENATAL X-RAY IRRADIATION ON AUDIOGENIC SEIZURES IN THE RAT

Abstract Gravid albino rats of the Sprague-Dawley strain received 25, 50, or 100 r whole-body X-ray irradiation on days 5, 10, 15, or 20 of gestation. Controls were sham-irradiated. Over 500 surviving offspring were evaluated for susceptibility to audiogenic seizures under two conditions of threshold testing, with the bell alone and with a pretreatment of Metrazol (16 mg/kg). The tests were conducted when the animals were 120 and 122 days of age. Irradiation on days 5 or 10 of gestation resulted in a decrease in seizure responses, while irradiation on days 15 or 20 of gestation resulted in an increase in seizure responses. The differences were more pronounced under the lowered threshold condition. These findings appeared to be independent of dosage. It was concluded that low levels of prenatal irradiation can alter the threshold of susceptibility to audiogenic seizures in the offspring.

Febrile Convulsions in Infant Rats, and Later Behavior

At 3 days of age, rats were (i) subjected to a febrile convulsion, or (ii) were handled, or (iii) were not handled. Evaluation at 30 days of age revealed that animals in the first group were heaviest and most resistant to audiogenic seizure stimuli. No differerences were found in maze-learning ability or activity level.

POSTNATAL EFFECTS OF CONTROL FLUIDS ADMINISTERED TO GRAVID RATS

Studies of the effects of drugs and other compounds on animals typically employ injections of the diluting agent to a control group. Diluting agents commonly used are distilled water, saline, and oil. Routes of administration also vary and include the intraperitoneal, subcutaneous, intravenous, and oral. Since previous work in this laboratory has been concerned with the administration of various pharmacologicall agents to pregnant rats and the effects on the behavior of che offspring (Werboff, Gottlieb, Havlena, & Word, 1961; Werboff, Gottlieb, Dembicki, & Havlena, 1961), ic was advisable to invescigate the differences, if any, between the control fluids and routes of administration currently in use. This investigation was undertaken to compare the effects of two control fluids (isotonic saline and distilled water) administered by two different routes (subcucaneous and intraperitoneal) to pregnant rats on the behavior of the offspring.

Postnatal effect of antidepressant drugs administered during gestation.

In a previous study, iproniazid administered to rats during the second trimester of gestation resulted in 100 per cent neonatal mortality. This report compares the effects of iproniazid and isocarboxazid administered prenatally on neonatal mortality and susceptibility to audiogenic seizures. Gravid albino rats of the Sprague-Dawley strain were randomly divided into a control and two drug groups. In every group, the treatment was administered intraperitoneally during one trimester of gestation on days 5 through 8, 11 through 14, or 17 through 20. The control group received 0.5 ml distilled water while the drug groups received either iproniazid (Marsilid, Hoffman-LaRoche) at 8.0, 4.0, or 2.0 mg/kg, or isocarboxazid (Marplan, Hoffman-LaRoche) at 4.0, 2.0, or 1.0 mg/kg. A total of 1047 offspring were born. Neonatal mortality was evaluated daily from birth through 30 days of age. At 45 and 47 days of age respectively, audiogenic seizure stimuli were administered under two conditions of threshold testing. Iproniazid was found to be significantly more toxic to neonatal survival than isocarboxazid or distilled water. Iproniazids effect was uniform throughout all trimesters of gestation, while isocarboxazid was most toxic in the first trimester. Distilled water administered as a control was found to be extremely toxic in the third trimester. Findings were independent of level of dosage. Offspring of both drug groups gave significantly fewer seizure responses than control offspring. The prenatal administration of these antidepressant drugs had a profound effect on neonatal mortality and susceptibility to audiogenic seizures.

Maze learning and open field behavior of adrenalectomized rats

Abstract Fifteen albino male rats were divided into three groups of five each: adrenalectomized, sham-operated control, and normal control. They were tested for learning ability on a four-unit T-maze (12 days after operation) and for activity level and “emotionality” in an open field (25 days after operation). Total body-weight and water intake were also recorded. There were no differences between groups in total body-weight, water intake, or ambulation in the open field. In the maze, however, early in learning controls made more errors than adrenalectomized animals. Later in maze learning the groups did not differ in number of errors, but the controls ran more quickly than the adrenalectomized animals. It is suggested that the intact animals are more reactive to the mild fear situation posed by the unfamiliar apparatus. This is supported by the fact that the adrenalectomized animals made fewer “emotional” responses in the open field situation than the controls.

Adrenalectomy of the Pregnant Rat and Behavior of the Offspring

Albino rats were adrenalectomized on either Day 10½ or Day 16½ of gestation. The offspring were reared by foster mothers. At 25, 30, 35, 40, or 45 days of age they were evaluated on the open field and timidity box tests. There were no behavioral or adrenal size differences among the offspring of adrenalectomized and sham-operated or unoperated control mothers. Consistent and significant sex differences on all measures were found, with females showing higher activity, greater emotionality, and larger adrenal glands than the males.

Effects of Overlearning and Spatial Delay of Reinforcement upon a Discrimination Reversal

Rats were trained on a brightness discrimination task under two conditions of spatial delay of reinforcement. Groups received either 0 or 150 postcriterial trials and then were given reversal training. Reversal training was under either the same delay as experienced in original learning or the alternate one. The results indicated that the delay variable, ineffective in original learning, affected reversal acquisition. The postcriterial trials had no affect on trials to reversal criterion. Further analysis indicated that overtraining resulted in a greater number of initial responses to the originally positive stimulus early in reversal training.