extraction-and-dissection-of-the-domesticated-pig-brain

Extraction and Dissection of the Domesticated Pig Brain

Use of the pig as a preclinical and translatable animal model has been well-documented and accepted by research fields investigating cardiovascular ...

University of Illinois at Urbana-Champaign

Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting that the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest that developmental PCB exposure can alter the interoceptive cues of psychostimulants.

Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs).

PCBs have long been known to affect dopamine (DA) function in the brain. The current study used an amphetamine behavioral sensitization paradigm in rats developmentally exposed to PCBs. Long-Evans rats were given perinatal exposure to 0, 3, or 6mg/kg/day PCBs and behavioral sensitization to d-amphetamine (AMPH) was assessed in one adult male and female/litter. Non-exposed (control) males showed increasing locomotor activity to repeated injections of 0.5mg/kg AMPH, typical of behavioral sensitization. PCB-exposed males showed greater activation to the initial acute AMPH injection, but sensitization occurred later and was blunted relative to controls. Sensitization in control females took longer to develop than in the males, but no exposure-related differences were observed. Analysis of whole brain and serum AMPH content following a final IP injection of 0.5mg/kg revealed no differences among the exposure groups. Overall, these results indicated developmental PCB exposure can alter the motor-stimulating effects of repeated AMPH injections. Males developmentally exposed to PCBs appeared to be pre-sensitized to AMPH, but quickly showed behavioral tolerance to the same drug dose. Results also revealed the behavioral effect was not due to exposure-induced alterations in AMPH metabolism following PCB exposure. 

Developmental exposure to polychlorinated biphenyls reduces amphetamine behavioral sensitization in Long-Evans rats.

Age-related declines in cognitive function can impair working memory, reduce speed of processing, and alter attentional resources. In particular, menopausal women may show an acceleration in the rate of cognitive decline as well as an increased vulnerability to brain diseases as estrogens may play a neuroprotective and neurotrophic role in the brain. To treat menopausal symptoms, many women turn to botanical estrogens that are promoted as a safe and natural alternative to traditional hormone replacement therapy. However, the majority of these compounds have not been systematically evaluated for efficacy and safety. The current study investigated the efficacy of the commercially available botanical estrogenic compound isoliquiritigenin (ISL) to alter performance on an operant working memory task, delayed spatial alternation (DSA). ISL is a compound found in licorice root that has been shown to have a wide range of effects on different biological systems, including estrogenic properties. This botanical is currently being used in over the counter dietary supplements. Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0 mg, 6 mg, 12 mg or 24 mg of ISL 60 min before testing on the DSA task. The DSA task required the rat to alternate its responses between two retractable levers in order to earn food rewards. Random delays of 0, 3, 6, 9 or 18 s were imposed between opportunities to press. ISL treatment failed to alter DSA performance. Previous work from our research group has found that estrogenic compounds, including 17β-estradiol and the botanical estrogen genistein impair performance on the DSA task. The goal of our botanical estrogens research is to find compounds that offer some of the beneficial effects of estrogen supplementation, without the harmful effects. This work suggests that ISL may not carry the cognitive risks associated with most other estrogenic compounds tested to date.

The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation.

This study investigated the efficacy of components of licorice root to alter performance on two different recognition tasks, a hippocampus-sensitive metric change in object location (MCOL) task and a striatum-sensitive double object recognition (DOR) task. Isoliquiritigenin (ISL), licorice root extract (LRE), and whole licorice root powder (LRP) were assessed. Young adult female rats were ovariectomized (OVX) and exposed to ISL, LRE or LRP at 0.075%, 0.5% or 5% respectively in the diet. An estradiol group was included as a positive control based on our prior findings. Rats were allowed to explore two objects for three 5-min study trials (separated by 3-min intervals) before a fourth 5-min test trial where the objects were moved closer together (MCOL task) or replaced with two new objects (DOR task). Rats typically habituate to the objects across the three study trials. An increase in object exploration time in the test trial suggests the rat detected the change. Estradiol improved MCOL performance and impaired DOR performance, similar to previously shown effects of estradiol and other estrogens, which tend to improve learning and memory on hippocampus-sensitive tasks and impair striatum-sensitive cognition. LRP had no effect on recognition while exposure to ISL and LRE improved MCOL performance. Exposure to ISL, LRE and LRP failed to attenuate DOR, contrary to effects of estradiol shown here and to previous reports in young-adult OVX rats. These findings suggest components of licorice root may prove to be effective therapies targeting memory enhancement without unintended deleterious cognitive effects.

Article	Year
Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs). Neurotoxicology and teratology\| PubMed ID: 20933596	2011
Developmental exposure to polychlorinated biphenyls reduces amphetamine behavioral sensitization in Long-Evans rats. Neurotoxicology and teratology\| PubMed ID: 23623962	2013
The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation. Neurotoxicology and teratology\| PubMed ID: 29408209	2018
Licorice root components mimic estrogens in an object location task but not an object recognition task. Hormones and behavior\| PubMed ID: 29920269	2018

Supida Monaikul

Biography

JoVE Journal Publications

Other Publications