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G Brosnan-Watters

Publications and source records attributed to G Brosnan-Watters.

6 recordsLinked to original sources
PubMed2000

Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms.

Animals↗
PubMed1999

Parallel recovery of MK-801-induced spatial learning impairment and neuronal injury in male mice.

The relationship between spatial learning impairment and reversible neuronal injury in the posterior cingulate/retrosplenial (PC/RS) cortex induced by MK-801 in male mice was studied using a four-corner holeboard task. Mice were dosed with 1 mg/kg MK-801 and tested on acquisition of a new "baited" hole at 5 or 12 h posttreatment. Acquisition in drugged mice was impaired at 5 h, but not at 12 h posttreatment. Their retention performances were unaffected 24 h after either the 5 or 12 h posttreatment acquisition sessions. MK-801 (1 mg/kg) was found to induce locomotor hyperactivity and some sensorimotor impairment at 5 h posttreatment. which could have contributed to the acquisition deficit. However, nonassociative effects of the drug were not prominent because this same dose did not impair holeboard performance at 5 h posttreatment when the task was well learned. Histologic experiments showed that many injured neurons (containing cytoplasmic vacuoles) were present in the PC/RS cortex at 5 h posttreatment but the reaction was essentially reversed at 12 h posttreatment. The results suggest that the acquisition impairment and neuronal injury induced by MK-801 evolve and recover in parallel according to a similar time schedule.

Analysis of Variance↗
PubMed1997

A rotating holeboard procedure for testing drug effects on spatial learning and memory in mice.

A procedure is described herein for evaluating drug effects on acquisition and retention of a spatial learning task in mice. The rotating holeboard apparatus is a rectangular open field containing four open holes arranged in either a four-corner or a row configuration. A mouse is trained to poke its head into a hole and retrieve a food reward from a 'baited' hole which contains a reward on every trial. A massed trials protocol is used where mice are required to learn a reference (trial-independent) memory task in a single session. A retention test is administered 24 h after acquisition. Prominent distal cues are present in the testing room and reliance on proximal visual, olfactory, or tactile cues for locating the baited hole is precluded by rotating the maze on each trial.

Animals↗
PubMed1996

MK-801 neurotoxicity in male mice: histologic effects and chronic impairment in spatial learning.

Several histological and behavioral experiments were conducted to investigate the neurotoxic effects of MK-801 in male mice. Moderate subcutaneous (s.c.) doses of MK-801 (0.5 and 1.0 mg/kg) induced the formation of intracytoplasmic vacuoles in pyramidal neurons in layers III and IV of the posterior cingulate/retrosplenial (PC/RS) cortex in 50% and 100% of the mice from the two respective treatment groups. Electron microscopic analysis of the vacuoles indicated that mitochondria and endoplasmic reticulum are the cellular organelles most prominently involved in this pathomorphological change. Treating mice with a high systemic dose of MK-801 (10 mg/kg s.c. or intraperitoneal (i.p.)) caused selective, irreversible degeneration of a small number of PC/RS cortical neurons. Compared to saline controls, the acquisition performance of mice treated i.p. with 10 mg/kg MK-801 was chronically impaired on a spatial learning task (modified hole board food search task) when tested at several posttreatment intervals (up to at least 5 months), although the groups did not differ on activity or sensorimotor tests conducted 2 weeks posttreatment. In summary, MK-801 caused histopathological changes in the mouse brain similar to those observed in the rat. Furthermore, high dose MK-801 treatment that killed a small number of mouse PC/RS cortical neurons resulted in a chronic acquisition impairment in spatial learning, an effect not previously demonstrated in any species.

Animals↗
PubMed1996

Acute behavioral effects of MK-801 in the mouse.

The acute effects of 0.05 mg/kg MK-801 on spatial learning and memory in male mice were studied using a modified hole board food search task. Dose-response sensorimotor and activity tests suggested that this dose of MK-801 did not induce significant nonassociative effects. Mice were trained on the hole board using a massed trials protocol to learn the location of a hole baited with a food reward among four corner holes. Retention was tested 24 h later. Mice were split into two groups matched according to acquisition scores. The following week, mice injected with 0.05 mg/kg MK-801 30 min before being trained to a different baited hole were significantly impaired in acquiring a new baited hole location compared to saline-treated mice, although retention performance was unaffected. The same result was found in another experiment in which treatments were crossed over, and a different version of the task was used. However, in another experiment, 0.05 mg/kg MK-801 did not impair performance when the hole board task was well learned.

Animals↗