Mechanical impacts to the skulls of rats produce specific deficits in maze performance and weight loss: evidence for apoptosis of cortical neurons and implications for clinical neuropsychology.

The purpose of this experiment was to induce closed head injuries that might be applicable to clinical neuropsychology. Six adult female albino rats were struck over the right dorsal skull by a 200-gm weight that fell through a 0.9-m tube while another six rats served as controls. The rats that received the impact to the skulls displayed significantly more weight loss and fewer completions of the maze during the subsequent two to four days (effect size about 40%) while their open field behaviors, response latencies to thermal stimulation of the feet, and immobility within a conditioned fear setting did not differ significantly from those of controls. Histological analyses of the brains about 35 days after the impact indicated striking alterations in the morphology of cerebral cortical neurons, strongly suggestive of an apoptotic-like process, within the dorsal cerebral cortices below the likely impact site. Distributions of clusters of these aberrant-looking cells were also evident opposite to the impact site within the ventral cerebrum. Because apoptosis is involved with minimal inflammation and edema, detection of diffuse apoptosis by MRI and CT would be unlikely even though the influence on adaptability would be significant.

Learning and memory in agmatine-treated rats.

Agmatine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, was examined for its role in water maze place learning, contextual and auditory-cued (discrete) fear learning and conditioned taste aversion learning, when administered systemically. Male Wistar rats were given saline or 1, 5, 10 or 50 mg/kg agmatine ip 20 min prior to or 30 min following daily training sessions in a hidden-platform (place learning) water maze task. Agmatine did not affect latencies to find the hidden platform or preference for the training quadrant during probe trials. When administered 20 min prior to contextual or auditory-cued fear-conditioning sessions, these doses of agmatine evoked a linear dose-dependent impairment in the magnitude of learned fear to the contextual stimuli when assessed during extinction trials 24 h later, but had no effect on the magnitude of learned fear to the auditory stimulus. Inferences of baseline motor activity and ability to respond to the presentation of footshock stimuli were not affected by the treatment. Injections of 50 mg/kg agmatine concurrently with a malaise-evoking agent following presentations to a novel sucrose solution abolished learned taste aversions; this agent did not evoke conditioned taste aversions alone. These studies indicate that systemically administered agmatine selectively impairs behavioral inferences of specific types of learning and memory.