Biomedical subjects

B J Hoplight

Publications and source records attributed to B J Hoplight.

15 recordsLinked to original sources

PubMed2006

Cocaine increases 5-HT1B mRNA in rat nucleus accumbens shell neurons.

Serotonin 5-HT(1B) receptors modulate behavioral responses to cocaine, but the effects of cocaine on endogenous 5-HT(1B) receptor expression are not known. Therefore, we examined the effect of binge cocaine administration on 5-HT1B mRNA expression in rat brain. We found that chronic, but not acute, binge cocaine exposure increased 5-HT(1B) mRNA by approximately 80% in nucleus accumbens shell and dorsal striatum. Surprisingly, 5-HT(1B) mRNA was increased in nucleus accumbens shell after chronic vehicle treatment as well, but this effect was driven by animals that were housed with cocaine-treated animals. Thus, 5-HT(1B) mRNA is upregulated by repeated exposure to cocaine and perhaps by social stress as well; both of these factors are relevant to the risk for relapse in cocaine addiction.

Analysis of Variance↗

PubMed2006

Increased expression of 5-HT1B receptors in rat nucleus accumbens via virally mediated gene transfer increases voluntary alcohol consumption.

Serotonin 5-HT(1B) receptors have been linked to alcoholism in humans and alcohol consumption in rodents. We hypothesize that these receptors, which are located on the axon terminals of nucleus accumbens' (NAcc) projection neurons, modulate alcohol reward mechanisms. To test this hypothesis, we measured ethanol consumption by rats that received bilateral microinjections of a viral vector producing 5-HT(1B) overexpression (HA1B/GFP). Other groups received either control (GFP-only) herpes simplex viral vectors into the medial NAcc shell or were handled briefly with no surgery. All animals were housed singly and had continuous access to water, 6% ethanol, and 12% ethanol in their home cages both before and after surgery. There were no differences in the amount or rate of weight gain, amount of food eaten, or total fluid consumed. There were also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the HA1B/GFP group consumed twice as much ethanol as the other groups. The main effect of total ethanol consumption was significant (p<.05); the control groups did not differ from each other. Whereas there were no between-group differences in 6% ethanol consumption, there was a large increase in the amount of 12% ethanol consumed by the HA1B/GFP-expressing animals compared to the two control groups as well as to their own presurgery intake (p<.05). We hypothesize that increased 5-HT(1B) expression in NAcc led to either greater reward or reduced aversive effects from the 12% ethanol, thereby leading to increased voluntary ethanol consumption.

Alcohol Drinking↗

PubMed2005

The effects of SB 224289 on anxiety and cocaine-related behaviors in a novel object task.

Cocaine facilitates dopamine transmission from ventral tegmental area (VTA) neurons that project to nucleus accumbens (NAcc), and previous experiments suggest that serotonin-1B (5-HT1B) receptors are involved in this effect. Specifically, activation of 5-HT1B receptors in VTA during cocaine exposure increases dopamine release in NAcc and enhances cocaine-induced locomotor activity, reward, and reinforcement. Thus, it is reasonable to hypothesize that blocking 5-HT1B activity may have the opposite effect. To investigate this hypothesis, SB 224289, a highly selective 5-HT1B antagonist, was used to block this receptor. In an open field/novel object exploration test, SB 224289 reduced cocaine-induced locomotion. However, SB 224289 also increased anxiety-like behavior, both alone and in combination with cocaine. This experiment gives evidence that 5-HT1B antagonists may reduce some of the behavioral effects of cocaine, but may have negative effects on anxiety as well.

Animals↗

PubMed2001

Effects of ectopias and their cortical location on several measures of learning in BXSB mice.

About half of BXSB/MpJ-Yaa mice have ectopias, which are misplaced clusters of neurons located in layer I of cortex. This study replicated several previous findings showing that there are learning differences between mice with ectopias and those without. In addition, we had sufficient numbers of ectopic mice to investigate if ectopics learned differently depending on the cortical location of the ectopia(s). Mice with at least one ectopia located in prefrontal cortex were initially impaired in learning the Morris maze, as well as relearning the Lashley maze when it was inverted, but learned better in the radial-arm maze when compared to ectopic mice with ectopias located in nonprefrontal regions of cortex. Mice with at least one ectopia in motor cortex learned the Lashley maze better than mice with ectopias located outside motor cortex. In sum, the cortical location of the ectopia(s) affected learning performance in certain tasks within the ectopic group, but regardless of the cortical location of the ectopia(s), ectopics still learned differently than nonectopics in several tasks.

Animals↗

PubMed2001

Effects of neocortical ectopias and environmental enrichment on Hebb-Williams maze learning in BXSB mice.

Approximately 40-60% of BXSB mice have neocortical ectopias, a developmental anomaly characterized by migration of neurons into the neuron-sparse layer I of cortex. Previous studies have shown that ectopic BXSB mice have superior reference, but inferior working, memory on spatial tasks. Female BXSB mice were housed either in an enriched environment or in standard cages at weaning. Subsequently, these animals were tested on four of the Hebb-Williams mazes in a water-based version of this maze. Theoretically, two of the maze configurations placed greater emphasis on reference memory to find the goal, whereas the other two favored working memory. Ectopics reared in standard housing conditions were better than nonectopics on mazes that favored the use of reference memory, but poorer on mazes that favored working memory. In contrast, subjects raised in the enriched environment showed no ectopia differences. A comparison of enriched and standard housing conditions found that the enriched animals had better reference memory but poorer working memory. The latter effect may be because the enriched environment, although more stimulating, did not change in time or space; and other researchers have shown that daily replacement of stimuli in complex environments is correlated with better working memory.

Animals↗

PubMed2000

Spatial ability of XY sex-reversed female mice.

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.

Animals↗

PubMed2000

Effects of the non-pseudoautosomal region of the Y-chromosome on behavior in female offspring of two congenic strains of mice.

The learning behavior of female offspring of two strains of mice congenic for the Y-chromosome, BXSX/MpJ-Yaa and BXSB/MpJ-Yaa+, was examined. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the fathers' Y-chromosome can indirectly affect their daughters' behavior. Approximately half the mice had neocortical ectopias, and females from the two paternal groups reacted differently to the presence or absence of ectopias. Since females do not have a Y-chromosome, these effects must be through non-genetic mechanisms. Prenatal factors that could have played a role include possible differences in gonadal growth and the presence of different H-Y antigens. Postnatally, the sires and male siblings of the two strains may not have behaved the same toward the female offspring and/or the dams, creating differences in behavior. In summary, the behavior of female offspring of two groups of males, genetically the same except for their Y-chromosomes, was examined. Since females do not receive a Y-chromosome from their fathers, in theory their behavior should not differ. Significant differences were found, indicating that the Y-chromosome, through some indirect mechanism, can affect females of the next generation.

Animals↗

PubMed1998

The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning. Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors.

Animals↗

PubMed1998

The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning, Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors.

Animals↗

PubMed1998

Water version of the radial-arm maze: learning in three inbred strains of mice.

The conventional land radial-arm maze has several disadvantages, including requiring a complicated automated apparatus, the elimination of odors as cues, and the use of food deprivation. We have created a water version of the maze, based on the principles of the land version, which maintains the advantages and excludes some of the disadvantages. In our maze, BXSB and C57BL/6 mice significantly reduced the number of working and reference memory errors committed over sessions, while NZB mice did not. For each strain, as the working memory 'load' increased during a session, the number of errors increased. However, with practice the BXSB and C57BL/6 strains were able to handle this memory load more effectively. Mice were able to learn the maze without extensive adaptation, training, or testing and they did not exhibit 'chaining'. This maze can also be considered to be an example of a water win-shift task that mice can easily learn. Therefore, the water version of the radial-arm maze can be a simple and useful tool for studying rodent learning and memory.

Animals↗

PubMed1998

Learning in year-old female autoimmune BXSB mice.

BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease. Approximately 40-60% of these animals show ectopic clusters of neurons in Layer I of cortex similar to those found in postmortem analyses of human dyslexics, and all exhibit an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans. The expression of immune disease in the BXSB strain, unlike in humans, is more severe in males than females. Most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age, when the BXSB females (unlike the male BXSB and female and male NZBs) are not yet showing high titers of autoantibodies associated with their lupus-like form of autoimmune disease. This study examined the behavior of BXSB females at an age subsequent to autoimmune disease onset. When contrasted with younger animals, year-old BXSB females showed good learning behavior, with no differences in Lashley maze learning and remarkably good performance in a visual discrimination learning task. These results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease. Results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in Lashley maze learning. Animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures. These findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals.

Age Factors↗

PubMed1996

Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.

Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.

Analysis of Variance↗

PubMed1996

A computer-aided procedure for measuring Hebb-Williams maze performance.

We describe a shortened procedure for testing mice over a 5-day interval on a swimming version of the Hebb-Williams maze. The mice are given 1 day of adaptation training, and are tested over the next 4 days on Hebb-Williams problems 1, 6, 12, and 5, in that order. As an animal swims through one of the maze problems, the computer screen shows the maze pattern, and an observer traces the path taken with a computer mouse. The computer program, Observe Software, stores the path sequence, determines the error score for that trial, and sends the information to a spreadsheet where it is available for statistical analyses.

Animals↗

PubMedDate not supplied

Working memory deficits in BXSB mice with neocortical ectopias.

Approximately 40-60% of BXSB/MpJ-Yaa mice exhibit neocortical ectopias, which are misplaced clusters of neurons in layer I of cortex. These ectopias are usually located in the prefrontal and/or motor region of cortex in BXSB mice, and are similar in appearance to those found in postmortem analyses of the brains of dyslexic humans. Several within-strain learning differences between mice with ectopias and those without have been reported. In particular, ectopic BXSB mice exhibited superior reference memory learning, but inferior working memory learning in several studies from our laboratory. This study used the Morris water maze delayed matching-to sample task and the water radial-arm maze to asses working memory in female BXSB mice with and without ectopias. In the delayed matching-to sample task, a hidden escape platform remained in a constant position for each four-trial session, but changed position between sessions. Trial 2 was the measure of working memory, i.e., how well did the mouse remember where the platform was located for that session. In the water version of the eight-arm radial maze, hidden escape platforms were located in four of the eight arms, and each platform was removed from the maze once found. This enabled us to assess working and reference memory simultaneously. Ectopic mice demonstrated working memory deficits during the first part of the delayed matching-to sample task compared to nonectopics. Similarly, ectopics made more working memory errors during the latter half of radial-arm maze testing, while not differing from nonectopics in reference memory performance. Additionally, there were significant correlations between measures of working memory in the radial-arm maze and working memory in a delayed matching-to-sample task. These findings are in agreement with other studies demonstrating working memory deficits in ectopic BXSB mice.

Animals↗

PubMedDate not supplied

In two species, females exhibit superior working memory and inferior reference memory on the water radial-arm maze.

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.

Animals↗