Biomedical subjects

S A Farr

Publications and source records attributed to S A Farr.

14 recordsLinked to original sources

PubMed1998

The pharmacology of post-trial memory processing in septum.

The septum is recognized as important in learning and memory, but relatively little is known about the role of specific neurotransmitter receptors in memory processing in the septum. We evaluated the role of the classical neurotransmitters in mice that were prepared for intraseptal microinfusion of drug solution after footshock avoidance training in T-maze. Retention for the footshock training was determined 1 week after training and drug administration. The results indicated that receptor agonists of dopamine, norepinephrine, glutamate and acetylcholine improved retention, while the antagonists impaired retention. Receptor agonists of serotonin, gamma-amino butyric acid (GABA) and opioids impaired retention, while antagonists improved retention.

Acetylcholine↗

PubMed1997

Sociosexual behaviour and paternity in procarbazine-exposed rats with or without regional testicular circulatory isolation.

Male Sprague-Dawley rats were used in two experiments in which a procarbazine bolus (400 mg kg-1 body mass) was administered with or without testicular circulatory isolation in the form of brief clamping of the spermatic cord and gubernaculum during drug administration. Separate tests of aggressiveness, sexual motivation, copulatory performance and paternity over the subsequent 6 weeks were used to assess functional changes resulting from testicular circulatory isolation. Experiment 1 compared intermale aggression and sexual motivation of animals in groups receiving procarbazine plus testicular circulatory isolation lasting 0, 15 or 45 min with that of animals in control groups with no clamp and no drug. Experiment 2 used a 2 x 2 factorial design to evaluate sexual performance and resulting paternity in animals 2 months after testicular circulatory isolation and drug exposure compared with that in control animals. Procarbazine treatment induced minimal disruption of normal interest in a receptive female, copulatory measures (intromissions or ejaculations) and structural integrity of seminal vesicles, bulbospongiosus muscles and ventral prostate glands. Animals exposed to the drug without testicular circulatory isolation were significantly less aggressive than animals in other groups. The most profound influence of procarbazine was on paternity. Males exposed to procarbazine with or without testicular circulatory isolation impregnated notably fewer females than did control males that were not exposed to the drug. There was no evidence of recovery of normal fertility up to 10 weeks after exposure to the drug. In conclusion, the deleterious influence of procarbazine on androgen-sensitive processes appears to be specific to intermale aggression and to fertility. The testicular circulatory isolation technique, for 45 min in particular, softened the impact of the drug on social behaviour, although procarbazine suppressed fecundity even with testicular circulatory isolation.

Animals↗

PubMed1996

Effect of chronic oral pentoxifylline administration on murine erythrocyte deformability.

BACKGROUND: Pentoxifylline has been reported to increase radiation sensitivity in vivo. We sought to evaluate whether this effect is mediated by changes in murine erythrocyte flexibility. METHODS: Pentoxifylline was administered via liquid or solid diet to young adult male CF-1 mice for 1-6 weeks. After 1, 3, and 6 weeks of drug administration, plasma levels of pentoxifylline and major derivatives were measured and erythrocyte deformability was assessed by rheoscopy, a technique which permits direct measurement of individual cellular dimensions. RESULTS: Contrary to prior reports, we found no discernible effect of the drug on erythrocyte deformability. CONCLUSIONS: The beneficial effect of pentoxifylline administration on radiation sensitivity in tumor-bearing mice is mediated by other mechanisms.

Administration, Oral↗

PubMed1996

Isatin inhibits food intake in mice.

Isatin (2,3-dioxindole) is an endogenous compound which is distributed throughout the central nervous system. The studies reported here demonstrate that isatin decreased food intake in food deprived TAC (SW) male mice 12-16 weeks of age. Isatin was more effective at decreasing food intake when the mice had to work harder to obtain food. Isatin also decreased sucrose, milk and water intake. When hunger was reduced by prefeeding milk to the mice, isatin was more effective at decreasing food intake. Isatin did not alter spontaneous activity in an openfield. Behaviors observed in the home cage indicated that mice which received isatin approached the food more often without eating than the controls. Movement in the home cage was significantly reduced in mice receiving isatin. Drinking, grooming and resting were not significantly affected by administration of isatin. These studies suggest that isatin may be an endogenous modulator of food intake.

Animals↗

PubMed1996

Peripherally administered calcitonin gene-related peptide decreases food intake in mice.

Previously, calcitonin gene-related peptide (CGRP) decreased food intake when administered ICV but not when administered peripherally to rats. Amylin, which has a close structural homology to CGRP, reduced food intake administered IP at concentrations higher than those previously tested for CGRP. We examined the effects of higher doses of IP-administered CGRP on food intake. CGRP reduced food intake from 25 to 200 micrograms/kg in mice. CGRP did not reduce water intake and was not aversive in a two-bottle test. Using a lever press, CGRP was more effective at reducing milk consumption in prefed than in nonprefed mice. The effect of CGRP on food intake was not antagonized by the cholecystokinin A receptor antagonist, L364,718. These studies suggest a role for CGRP as a satiating factor.

Analysis of Variance↗

PubMed1995

Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory.

Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.

Aging↗

PubMed1995

Effect of ovarian steroids on footshock avoidance learning and retention in female mice.

Mice were trained to avoid footshock in a T-maze, with retention tested one week later. Adult male CD-1 mice made their first avoidance during acquisition after fewer trials than random cycling females and with less variability. Female mice in diestrus, when plasma levels of progesterone are low, learned to avoid footshock faster than females in estrus. Ovariectomized (OVX) mice learned in fewer trials than intact random cycling mice. Similar differences, though of a smaller magnitude, were found on the retention tests (i.e. males had better retention than females, mice in diestrus showed better retention 8 days later when in the same part of the estrous cycle than those in estrus, and OVX mice had better retention than cycling females). OVX mice with estrogen implants learned faster than those with progesterone implants or progesterone plus estrogen implants. Hormonal status did not affect sensitivity to acoustic or footshock stimuli as measured by a startle reflex, nor did it affect activity. Pretraining administration of amphetamine, picrotoxin and strychnine attenuated the impairing effect of progesterone on acquisition. The possibility that progesterone may impair learning and to some extent, retention by facilitating the GABAergic activity and thereby reducing arousal level is discussed.

Animals↗

PubMed1995

Nitric oxide synthase inhibition and food intake: effects on motivation to eat and in female mice.

Recent studies have demonstrated that nitric oxide may play an important role in the regulation of food intake. The studies reported here extend these findings by demonstrating that NG-nitro-arginine-methylester, N-Arg(ME), a nitric oxide synthase inhibitor, decreased intake of a highly palatable substance (i.e., milk), though at a higher dose than necessary for decreasing consumption of food pellets. N-Arg(ME) failed to inhibit lever press for milk reward in nonprefed mice, but decreased lever pressing in prefed mice. N-Arg(ME) decreased food intake in female mice, being most potent in proestrus. These studies suggest that nitric oxide synthase inhibition decreases food intake without inducing aversion or illness.

Amino Acid Oxidoreductases↗

PubMed1995

Age-related impairment in learning but not memory in SAMP8 female mice.

Four-month and 12-month-old SAM (Senescence Accelerated Mouse)-P8 and -R1 female mice, either intact or ovariectomized, were trained to avoid foot shock in a T-maze. Mice were trained until they made their first avoidance. Memory retention of this task was then tested 1 week later. The results indicated that P8, but not R1, female mice whether intact or ovariectomized, showed an age-related learning impairment. This impairment was more apparent in ovariectomized mice, as ovariectomy was associated with a significant reduction in the mean trials to make an avoidance in all groups except 12-month P8 females. Of greatest interest was the absence of any age-related impairment of retention in P8 females. In several previous studies, SAM-P8, but not R1, males showed an age-related impairment of learning and memory. These results indicate that age-related impairment of memory in P8 mice may be inherited in a sex-related manner, and suggests that the mechanisms involved in the development of impaired learning and memory are different.

Aging↗

PubMed1995

Effects of amylin on appetite regulation and memory.

Amylin has been demonstrated to decrease food intake in mice and rats. Amylin is effective when delivered both peripherally and directly into the central nervous system. Amylin's effect on food intake is not aversive. Amylin may produce its effect on food intake by modulating nitric oxide synthesis. Calcitonin gene related peptide also decreases food intake after peripheral and central administration. In addition, amylin has been demonstrated to modulate memory at both peripheral and central sites.

Amyloid↗

PubMed1994

Testicular cytotoxicity of intravenous methotrexate in rats.

Although the testicular cytotoxicity of methotrexate has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of methotrexate (0-700 mg/kg body weight [BW]), with necropsy 56 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, modified Johnsen score, repopulation index, and epididymal index. Effects of methotrexate on heart, lung, liver, and kidney histology were evaluated qualitatively. Oligospermia occurred at low and intermediate dosages of methotrexate, but testicular atrophy was not observed. LD50 at day five for methotrexate appears to be approximately 300 mg/kg BW using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.

Animals↗

PubMed1993

Testicular circulatory isolation in man: comparison of radionuclide angiography with Doppler evaluation.

Testicular circulatory isolation (TCI) holds promise as a method to avoid drug-induced infertility in male patients about to receive cancer chemotherapy. Complete exclusion of blood flow to the testicle is essential to the success of this technique. We have compared the hand-held Doppler probe and radionuclide angiography (technetium-99m pertechnetate) as monitors of testicular blood flow in 10 patients subjected to unilateral TCI. When Doppler evaluation indicated that testicular circulation had been interrupted, the radionuclide angiogram uniformly confirmed and quantified this conclusion. These results validate the hand-held Doppler as an appropriate tool for assessing testicular blood flow in patients undergoing TCI.

Aged↗

PubMed1993

Regional procarbazine delivery reduces testicular toxicity.

Procarbazine has been implicated as a cause of infertility. Regionalization of drug delivery is a potential method to avoid this problem. We investigated the protective effect of testicular circulatory isolation (TCI) on gonadal toxicity during procarbazine administration in the Sprague-Dawley rat. Four groups (n = 10/group) were used. Animals in group 1 received no treatment. Rats in groups 2 and 3 were anaesthetized and received TCI of the left testis by clamping of the spermatic cord and gubernaculum immediately before a bolus of intravenous procarbazine (400 mg kg-1). The clamping was maintained for 15 min after procarbazine administration in group 2 and for 45 min in group 3. Rats in group 4 received sham surgery immediately before procarbazine administration. On day 70, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurements of testicular weight, sperm head count, repopulation index, and epididymal index. The results indicated that 15 min of TCI did not mitigate testicular toxicity; 45 min of TCI provided moderate protection against procarbazine-induced testicular toxicity.

Animals↗

PubMed1993

Serum levels of pentoxifylline and its metabolites in non-tumor-bearing mice after chronic oral pentoxifylline administration.

Pentoxifylline lowers blood viscosity and increases erythrocyte flexibility in patients with atherosclerosis, thus increasing tissue oxygen delivery. Since tumor neo-vessels are associated with tissue hypoxia, which contributes to failure of radiation therapy, pentoxifylline might also be useful as a radiation sensitizer. Such drugs are often evaluated in the murine model, but serum levels of pentoxifylline and its metabolites have not been determined in the mouse after chronic oral dosing. We investigated this by administering pentoxifylline via liquid diet or solid diet to young adult male CF1 mice for one to six weeks and assaying plasma for the parent drug and its metabolites. At one, three, and six weeks, plasma levels of pentoxifylline and major derivatives were consistently detectable. Mice remained healthy during this period, indicating that ingestion of large amounts of this drug is well tolerated.

Administration, Oral↗