Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints.

Administration, Oral↗

PubMedDate not supplied

A nonhuman primate version of the open field test for use in behavioral toxicology and teratology.

As reviewed here, little work has been done on testing nonhuman primates individually in open field paradigms. Hence, normative data from three studies of rhesus monkeys are presented. Important criteria for describing the pattern of activity exhibited by monkeys in the open field are introduced and the effects of gender and differences in rearing are assessed. Differences between this nonhuman primate version of the open field and that typically used with rodents are discussed, including reasons for differences in the variability of behavior between monkeys and rodents and a comparison of coefficients of detection (as an index of the power of the test to detect group differences). Overall, the use of the nonhuman primate version of the open field in behavioral toxicology and teratology is feasible and may fill a significant niche not presently well represented.

Animals↗

PubMedDate not supplied

Effects of postnatal lead exposure on open field behavior in monkeys.

Nursery-reared rhesus monkeys were treated with either no lead or moderate levels of lead from day eight or nine until day 365 after birth. All subjects were at or below 5 micrograms/dl blood lead levels for at least 1.5 years by the time of the present study conducted at 4 years of age. Data were collected in a primate version of the open field test which proved sensitive to several behavioral alterations in the lead-treated monkeys. These significant differences included a failure to habituate as evidenced by number of sectors entered, increased durations of activity and environmental exploration, and a longer latency to enter the open field. Most of these effects were compatible with a hypothesis of hippocampal dysfunction in the lead-treated monkeys and appeared to indicate enduring lead-induced alterations. These results provide further support for a correlation between early lead exposure and hippocampal dysfunction. Additionally, the utility of a primate version of the open field test for behavioral toxicological studies is substantiated.

Animals↗

PubMedDate not supplied

Effects of arecoline and scopolamine on open field behavior of adult monkeys treated with lead during the first year postpartum.

Nursery-reared rhesus monkeys were treated with no or moderate levels of lead during the first year postpartum. Previously, the lead-treated monkeys exhibited behaviors in the nonhuman primate version of the open field (10) resembling those caused by hippocampal lesions. The current study investigated the mechanism(s) underlying these lead-related effects using a cholinergic agonist (arecoline) and antagonist (scopolamine) as pharmacological probes that were administered prior to open field testing at 5 and 6 years of age, respectively. Arecoline decreased locomotion and number of sectors entered. Scopolamine decreased defecation frequency. Neither drug interacted with prior lead treatment, indicating limited cholinergic involvement in the expression of these alterations. The lead-treated subjects continued to exhibit alterations as previously reported (10); specifically, a longer latency to enter the open field, increased frequency and duration of environmental exploration and, at 5 years of age, decreased duration of inactivity in the open field. These effects were seen four and five years after lead treatment ended and nearly three and four years after blood lead levels had declined to less than or equal to 5 micrograms/dL. Although latency to enter and duration of inactivity seem to be approaching control levels, the increased exploration does not.

Animals↗

PubMedDate not supplied

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on behavior of monkeys in peer groups.

Adult female rhesus monkeys were fed diets containing 0, 5, or 25 ppt 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for approximately 4 years. They were bred to unexposed males during TCDD exposure (Experiment 1) and again after TCDD exposure ended (Experiment 2). Offspring from both experiments were weaned at 4 months and socialized for 1.5 h/day in groups of four monkeys each beginning at approximately 8 months of age. Each social group contained both control and TCDD-exposed monkeys. In Experiment 2, the offspring were later placed in new social groups containing only monkeys from the same TCDD exposure condition. The TCDD-exposed offspring born concurrent with maternal TCDD exposure (Experiment 1) initiated more rough-tumble play, retreated less during play bouts, and were less often displaced from preferred positions in the playroom. They also engaged in more self-directed behaviors. The behavior of offspring born after maternal TCDD exposure ended (Experiment 2) was not altered when they were socialized with control monkeys. However, some behavioral changes did emerge when they were placed in social groups containing only TCDD-exposed monkeys.

Animals↗

PubMedDate not supplied

Lack of effect of chronic developmental lead treatment on biogenic amines and metabolites in monkey cerebrospinal fluid.

Concentrations of 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in the cerebrospinal fluid (CSF) of control and chronically lead-treated nursery-reared rhesus monkeys sampled periodically from infancy through adulthood. Blood lead levels peaked at 62 micrograms/dl at 1.5 months of age, averaged 45 micrograms/dl for the remainder of the first year postpartum, and were maintained at 14 micrograms/dl from 20-58 months of age. Cisternal CSF samples were collected monthly from 5-35 months of age and every 1-4 months from 36-58 months of age. Biogenic amine and metabolite concentrations were assayed by high-performance liquid chromatography with electrochemical detection. Overall concentrations of DOPAC, HVA, NE, MHPG, and 5-HIAA were not significantly different in the control and lead-treated groups nor were there any significant interactions between lead treatment and age for any measure. DOPAC, HVA, and 5-HIAA concentrations decreased gradually with age, whereas MHPG concentration decreased sharply between 35 and 40 months of age. NE concentration remained stable across development.

Aging↗

PubMedDate not supplied

Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.

MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Home cage behavior and lead treatment in rhesus monkeys: a comparison with open-field behavior.

Nursery-reared rhesus monkeys were treated with no (n = 4) or moderate levels of lead (n = 4) during the first postnatal year. Mean blood lead levels peaked at 55 micrograms/dl at 5 weeks of age, averaged 36 micrograms/dl for the remainder of the first year postpartum, and declined to < or = 5 micrograms/dl for the 4 monkeys by 2.3 years of age. Previously, the lead-treated monkeys exhibited increased environmental exploration and decreased inactivity in a nonhuman primate version of the open field when tested at 4, 5, and 6 years of age (5,6). The current study was designed to assess behavior in the home cage of these monkeys at 6 years of age to determine: (a) whether the increased exploration was specific to the open field, and (b) any lead-related behavioral alterations specific to the home cage. Each monkey was observed twice weekly for 10 weeks and the duration and frequency of 17 behaviors were recorded. Lead treatment did not result in significant alterations in any of the six behaviors which occurred with enough frequency to warrant analysis. As a whole, all monkeys were either inactive or engaged in self-grooming for a large proportion of the test session. Less frequent were behaviors such as locomotion, environmental exploration, and self-directed behaviors. The distribution of behavioral activities in the home cage differed from that in the open field. Potential reasons for the expression of significant lead-related effects in the open field and not in the home cage are discussed as well as the differences in distribution of behavioral activities.

Animals↗

PubMedDate not supplied

Prenatal ethanol exposure in rats: long-lasting effects on learning.

Pregnant Sprague-Dawley rats were fed a liquid diet containing either 0% (group C), 18% (group L), or 36% (group H) ethanol-derived calories (EDC) from gestational day 1 to 20. Male offspring were assessed under a conditioned taste aversion paradigm (PND 35-45), in a complex maze (PND 68-80), and for operant behavior (temporal response differentiation and motivation to work for food, PND 140-198). Although conditioned taste aversion was fully acquired by all groups, retention of the conditioned taste aversion response was impaired in group H animals. Importantly, deficits in the acquisition of timing behavior were found in group H (group L not tested), confirming that this operant task is quite sensitive in detecting prenatal drug effects and demonstrating that neurological effects of prenatal ethanol exposure persist into late adulthood.

Animals↗

PubMedDate not supplied

Effects of acute treatment with dopaminergic drugs on open field behavior of adult monkeys treated with lead during the first year postpartum.

A pharmacological challenge of nonhuman primate open field behavior, similar to that which previously assessed the cholinergic system (10), was used here to measure potential lead-induced alterations in the dopaminergic system. Monkeys that had been treated with lead during the first year postpartum were assessed at 7 years of age in the open field after acute intramuscular injection of apomorphine (0.0-0.3 mg/kg) or haloperidol (0.0-30 micrograms/kg). Duration of environmental exploration indicated a possible greater responsivity to 0.2 mg/kg apomorphine in the lead-treated monkeys; however, in all other behaviors, lead-treated monkeys responded to both drugs similarly to controls. Regardless of lead treatment, apomorphine administration decreased duration of inactivity and increased environmental exploration; the latter possibly included an increase in stereotypical behavior that might have been recorded as environmental exploration. Haloperidol had no significant effects on open field behavior over the dose range tested. Open field behavioral alterations previously reported for these monkeys at 4-6 years of age were no longer strongly exhibited by the lead-treated monkeys in any portion of the current study. Latency to enter the open field was marginally increased in the lead-treated group but levels of environmental exploration were comparable to controls. These results indicate an attenuation of lead-related effects with maturity and/or familiarity with the open field.

Analysis of Variance↗