A rapidly learned odor discrimination task based on spontaneous foraging behavior of the rat was used to evaluate the role of N-methyl-D-aspartate (NMDA) receptors (NMDARs) in ongoing memory consolidation. Rats were trained in a single session to discriminate among three odors, one of which was associated with palatable food reward. Previous experiments showed that the NMDAR antagonist DL-APV induced amnesia for this task when injected immediately after training. In the present study, memory was reactivated 24 h after training by exposure to the rewarded odor within the experimental context after which rats received an intracerebroventricular injection of APV. Combined reactivation-drug treatment induced profound amnesia when tested 48 h later. Animals receiving drug alone, in absence of reactivation, showed perfect retention. It is concluded that NMDARs support a consolidation process taking place after memory reactivation.
The biochemical and cellular events that lead to secondary neural damage after traumatic brain injury (TBI) contribute to long-term disabilities, including memory deficits. There is a need to search for single and/or combined treatments aimed at reducing these TBI-related dysfunctions. The effects of citicoline and of voluntary physical exercise in a running wheel (3 weeks), alone or in combination, on TBI-related short-term (3 h) and long-term (24 h) object recognition memory (ORM) deficits, and on neurogenesis and neuroprotection were examined using a rodent model of TBI (controlled cortical impact injury). Citicoline improved memory deficits at the two times tested, while physical exercise only in the long-term test. Physical exercise had a clear neuroprotective effect as indicated by reduced interhemispheric differences in hippocampal formation and lateral ventricle volumes and in density of mature neurons in the hilus of the dentate gyrus and the perirhinal cortex. Physical exercise also increased cell proliferation and neurogenesis in the granular cell layer of the dentate gyrus. Some degree of neuroprotection of citicoline was suggested by reduced interhemispheric differences in the volume of the hippocampal formation. Contrary to what was expected, the effects of citicoline and physical exercise did not sum up.Furthermore, a negative interference between both treatments was found in several behavioral and histological variables. The promising profiles of both treatments as therapeutic tools in TBI when applied singly, underscore the need to carry out further works looking for other combined treatment regimens that increase the benefit of each treatment alone.4
The present experiments determined the consequences of blocking muscarinic cholinergic receptors of the prelimbic (PL) cortex in the acquisition and retention of an odor-reward associative task. Rats underwent a training test (five trials) and a 24-h retention test (two retention trials and two relearning trials). In the first experiment, rats were bilaterally infused with scopolamine (20 or 5 µg/site) prior to training. Although scopolamine rats showed acquisition equivalent to PBS-injected controls, they exhibited weakened performance in the 24-h retention test measured by number of errors. In the second experiment, rats were injected with scopolamine (20 µg/site) immediately or 1 h after training and tested 24 h later. Scopolamine rats injected immediately showed severe amnesia detected in two performance measures (errors and latencies), demonstrating deficits in retention and relearning, whereas those injected 1 h later showed good 24-h test performance, similar to controls. These results suggest that muscarinic transmission in the PL cortex is essential for early memory formation, but not for acquisition, of a rapidly learned odor discrimination task. Findings corroborate the role of acetylcholine in consolidation processes and the participation of muscarinic receptors in olfactory associative tasks.
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