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Biomedical subjects

B Gough

Publications and source records attributed to B Gough.

24 records · Page 2Linked to original sources
PubMedDate not supplied

Drug-induced circling preference in rats. Correlation with monoamine levels.

Drugs of abuse, such as phencyclidine (PCP), methamphetamine (METH), and cocaine (COC) are known to affect several behaviors in rats, such as motor activity, stereotypy, and circling. In this study, we evaluated whether these drugs produce circling preferences in the presence or absence of unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the caudate nucleus. Adult male CD rats were lesioned with 10 micrograms 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip) its congener (+) MK-801 (0.15 mg/kp, ip), METH (2 mg/kg, ip) COC (60 mg/kp, ip), or apomorphine (0.2 mg/kg, ip). Circling preference was recorded in control and lesioned rats for 2 h before animals were sacrificed to determined monoamine levels by HPLC/EC. In control animals, administration of these drugs produced 60-70% left circling. In lesioned animals, these drugs produced 78-90% ipsilateral (toward the lesion) circling, except apomorphine, which produced 60-80% contralateral (away from the lesion) circling. Dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations significantly decreased ipsilaterally in lesioned caudate nucleus (CN) and substantia nigra (SN). However, no significant changes were observed in nucleus accumbens (NA) and olfactory tubercles (OT). These data demonstrate that drugs of abuse like PCP, its congener (+) MK-801, METH, and COC produce a greater preference to turn toward the left than the right, a finding similar to that found in human psychosis. Since 6-OHDA lesions enhanced the circling bias and depleted DA and its metabolites DOPAC and HVA, it also suggests that the dopaminergic system may be involved in the circling behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats.

Prenatal maternal stress in rats and mice can demasculinize and feminize the sexual behavior of adult male offspring. Causal mechanisms are unknown, but one attractive hypothesis is that stress activation of maternal adrenal glucocorticoid secretion is the responsible agent. To test this hypothesis, pregnant rats were exposed to a variety of substances which enhance glucocorticoid actions. These included ACTH (20 IU of a gel preparation, SC once daily), corticosterone (CORT; 7 mg/kg SC in oil, three times daily), or dexamethasone (DEX; 0.1 mg/kg, SC once daily). Controls included noninjected dams and a positive stress control group (restraint under bright lights three times daily). All treatments reduced maternal weight gain, DEX most potently. No treatment altered litter size, stillbirths, or sex ratio, but DEX reduced weight at birth, an effect still seen at postnatal day 85. DEX, CORT, and stress reduced male adrenal weight at birth, while DEX and CORT altered sexual differentiation as measured by anogenital distance. Stress impaired adult male sexual performance but not the lordosis quotient following exposure of animals to stud males. DEX affected both measures. No other treatment had any significant effect on sexual behavior. No treatment altered plasma LH levels, either basal or in response to an estrogen challenge in adult gonadectomized males. In adulthood there was no treatment effect on stress reactivity, measured behaviorally or by plasma glucocorticoids. Correlational analysis revealed that weight gain during pregnancy was the single best predictor of subsequent sexual performance. It is concluded that prenatal dexamethasone exposure demasculinizes and feminizes male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMedDate not supplied

Postnatal methylazoxymethanol: sensitive periods and regional selectivity of effects.

Work on neonatal MAM exposure has focused primarily on exposure within the first week postpartum, and on resulting hypoplasia or stunting of the cerebellum. Rats in this study were exposed to MAM on 4 consecutive postnatal days (PND), beginning at one of six ages, from birth through weaning (PND 1, 5, 9, 13, 17, or 21). MAM was administered subcutaneously in doses of 3, 4, or 5 mg/kg twice per day. Rats were sacrificed at PNDs 28 or 84. The most sensitive age for MAM-induced stunting was determined to be PNDs 1-4. When 5 mg/kg MAM was administered twice daily on PNDs 1-4, body weight was reduced by 24% at age 28 days. Additionally, when compared to control rats, brains of the 28-day-old rats were stunted as follows: whole brain (11%), cerebellum (35%), hippocampus (11%), and olfactory bulb (27%). The effects of PND 1-4 MAM exposure were still evident at 84 days of age when cerebellum and olfactory bulbs from treated rats weighed 30% less than those same regions in control rats. These findings indicate that neonatal exposure to MAM results in permanent stunting in select regions of developing rat brain. This stunting, along with other known MAM effects, can be tailored by exposure age and dose to augment the use of MAM as a positive control for investigation of compounds with neurotoxic potential.

Age Factors↗
PubMedDate not supplied

Potential of machine-vision light microscopy in toxicologic pathology.

Major developments in machine-vision light microscopy and in reagent chemistry have led to a renaissance and revolution in the use of the light microscope in biology, biotechnology, and medicine. The potential use of this technology in the field of toxicologic pathology is discussed. It is suggested that a combination of investigating living cells and tissues and fixed samples using the new technologies will lead to understanding mechanisms of toxicity. Examples of the use of the methods in basic cell biology and medicine are presented.

Animals↗
PubMedDate not supplied

d-Amphetamine as a behavioral teratogen: effects depend on dose, sex, age and task.

Reports on the behavioral effects of prenatal exposure to d-amphetamine in rodents are inconsistent. Activity levels have been variously reported to increase, decrease, or show no change (as in the Collaborative Study) following such exposure. As a follow-up to the Collaborative Behavioral Teratology Study, 3 experiments have been conducted at the NCTR to examine the behavioral teratogenicity of this compound following SC dosing on days 12-15 of gestation. A higher dosage (3 mg/kg) was included and evaluations involved tasks used in the Collaborative Behavioral Teratology Study (startle, figure-8 activity) and other tasks not previously undertaken at the NCTR (short-term reactivity to novel open fields, intake of sweetened solutions). Activity measures gave especially mixed results. There was no effect of prenatal exposure, even at 3 mg/kg, upon longer-term activity, before or after amphetamine challenge, in figure-8 mazes or rectangular photocell chambers, at postnatal days (PND) 47 or 120. In one experiment, changes in reactivity to brief exposure to an open field daily over 3 days were seen in higher dosage PND 135 males but not females, while higher dosage females but not males showed lowered emergence latencies at this age. In a second experiment, no exposure-related changes were seen in reactivity to an open field in offspring of either sex at PND 47 or 70. Auditory startle amplitude showed complex dose effects in these two experiments. Females exposed to 3 mg/kg had elevated startle amplitude at PNDs 47 and 120, but not at PND 19. Males in the 3 mg/kg group had elevated startle at PND 19, but not thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗