Pilocarpine and physostigmine attenuate spatial memory impairments produced by lesions of the nucleus basalis magnocellularis.

Three experiments, with 63 male Long-Evans rats, investigated the effects of bilateral ibotenic acid-induced lesions of the nucleus basalis magnocellularis (NBM) on the acquisition and retention of several spatial memory tasks. Maintenance of spatial memory in a food-search task was impaired following NBM lesions. Acquisition of spontaneous alternation and reinforced alternation in a T-maze, but not the acquisition of a position habit, was also significantly impaired in Ss with these lesions. In several of the tasks, there was evidence of some learning in the lesioned Ss after substantial training, although they were significantly deficient when compared with controls. Intraperitoneal administration of the cholinergic agonists physostigmine sulfate (0.5 mg/kg) or pilocarpine nitrate (3 mg/kg) prior to behavioral testing resulted in a rapid and significant improvement in the performance of the lesioned Ss. Lesions significantly reduced the activity of choline acetyltransferase in the anterior and the posterior neocortex but not the hippocampus. Results indicate that the cholinergic projections originating in the NBM are involved in the learning and memory of spatial tasks. (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kynurenic acid protects against the neurochemical and behavioral effects of unilateral quinolinic acid injections into the nucleus basalis of rats.

Investigated whether unilateral coinjections of kynurenic acid (KYN) and quinolinic acid (QUIN) into the rat nucleus basalis magnocellularis (nbm) antagonized the effects of QUIN alone. Food-deprived rats were pretrained on an 8-arm radial maze, with four arms baited, until choice accuracy stabilized to ≥87% correct. Postoperatively, rats were tested on the radial maze for 32 consecutive days. Feeding behavior and locomotor activity were also measured to determine if nonassociative factors accounted for any observed behavioral deficits. QUIN lesions resulted in significantly more working and reference memory errors compared with sham-operated and coinjected animals, which did not differ significantly from each other. There were no reliable group differences in amount of food eaten or locomotor activity. The QUIN group had a reliable decrease in cortical choline acetyltransferase, with no significant changes for the sham and coinjected groups. Results confirm that KYN antagonizes the neurotoxic and mnemonic effects of QUIN alone and suggest that the memory deficits induced by nbm lesions cannot be solely attributed to changes in feeding or locomotor activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression does not aggravate the episodic memory deficits associated with Alzheimer's disease.

In a population-based study of persons between 75 and 96 years of age, normal old adults (n?=?296), patients with Alzheimer"s disease (AD; n?=?45), and patients with concomitant AD and depression (AD-D; n?=?9) were compared on free recall and recognition of slowly and rapidly presented words and digit span. With the exception of forward digit span, the normal old group outperformed the 2 AD groups across all tasks. In free recall, only the normal old group performed better as task pacing decreased; however, all groups benefited from more study time in recognition. This suggests that both AD and AD-D patients have deficits in the ability to use more study time for remembering. Of most importance, the 2 AD groups were indistinguishable for all task variables. This lack of comorbidity effects is discussed relative to the view that depression, much like many other individual-difference variables that affect memory performance in normal aging, may be overshadowed by the influence of the process in AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective memory impairments produced by transient lidocaine-induced lesions of the nucleus accumbens in rats.

Reversible lidocaine-induced lesions of the nucleus accumbens (NAC) impaired performance on the spatial win-stay, but not on the cued win-stay, radial arm maze task. Pretraining lesions on the former task did not affect foraging for 4 pellets during either the training or test phases. In contrast, lesions given prior to the test phase significantly disrupted retrieval of 4 pellets on the 8-arm maze. Comparable deficits also were observed in rats trained to forage for 4 pellets on an 8-arm maze without prior win-shift experience. State-dependent drug effects were ruled out by replicating the disruptive effects of lidocaine infusions into the NAC on spatial win-shift performance in rats receiving this treatment prior to both training and test phases. These results suggest that the NAC may interact with the hippocampus to guide foraging behavior requiring memory of previous spatial locations on a maze. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attentional momentum does not underlie the inhibition of return effect.

J. Pratt, T. M. Spalek, and F. Bradshaw (1999) recently proposed that attentional momentum is the mechanism underlying the inhibition of return (IOR) effect. They suggested that momentum associated with an attentional movement away from a peripherally cued location and toward an uncued opposite location is essential and fundamental to the finding of an IOR effect. Although it is clear from the present study and from a reanalysis of data from Pratt et al. that response time can be facilitated at an uncued opposite location, this putative effect of attentional momentum is neither robust nor reliable. First, it occurs for only a minority of participants. Second, it occurs in only a subset of the cued display positions. And finally, it is uncorrelated with the occurrence of IOR. Together the data indicate that the attentional momentum hypothesis is an overgeneralization and that it does not underlie the robust and reliable IOR effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of sleep parameters and memory in intact old rats and young rats with lesions in the nucleus basalis magnocellularis.

Relations between sleep and memory were examined as a function of aging in rats. Sleep (24 hr), passive avoidance retention, and choline acetyltransferase (CAT) activity were assessed in 3 age-groups (6, 15, and 24 months old). Age-related alterations were evident in sleep, memory, and cortical and striatal CAT activity. Retention deficits in old rats were significantly correlated with several measures of paradoxical sleep. Similar analyses in 6- and 15-month-old rats with ibotenic acid-induced lesions of the nucleus basalis magnocellularis (NBM) showed several alterations in sleep, memory, and cortical CAT activity comparable to those seen in the old rats. One measure of paradoxical sleep, bout duration, correlated significantly with retention scores in rats with lesions. Thus, fragmented paradoxical sleep accompanies memory impairments in old rats and in young rats with NBM lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reversible inactivation of the medial septum or nucleus basalis impairs working memory in rats: a dissociation of memory and performance

Lidocaine-induced inactivation of the medial septum immediately after training or prior to testing in a delay radial-arm maze task produced deficits in spatial working memory that reflected impaired acquisition of the task. Injection of lidocaine into the nucleus basalis magnocellularis produced a profile of behavioral changes that indicated that temporary inactivation of this structure impaired the behavioral expression of information already stored in working memory. This appears to reflect an impairment in processes that are required for performance (i.e., attention, motivation, sensorimotor function) of the task but not for retrieval of stored information. Site-specific inactivation of the basal forebrain should help to reveal the involvement of its component structures in different aspects of cognitive function.     

EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats

We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and ACh concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.     

Multisensory deficits in rats produced by acute exposure to cold swim stress.

Cold swim stress and morphine administration produce analgesia. Whether this was accompanied by changes in other senses was investigated. Analgesia was assessed with a tail-flick test; the sensitivity of the other senses was assessed using the ability of mild sensory stimuli (prestimuli) to inhibit the amplitude of a subsequently elicited acoustic startle response. In Experiment 1, auditory prestimuli were used. In Experiment 2, visual prestimuli were used. In each experiment, rats were exposed to cold-water swims followed by behavioral testing, warm swims followed by testing, and testing alone. This was repeated, substituting morphine injections followed by testing, vehicle injections followed by testing, or testing alone. Both cold swim stress and morphine produced reliable analgesia. Only cold swim stress interfered with the ability of the stimuli to inhibit startle. This reflects decreased sensitivity to auditory and visual stimulation caused by cold swim stress, which suggests that the resultant sensory deficits are more global than is currently believed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pretraining does not ameliorate spatial learning deficits induced by intrahippocampal infusion of AP5.

Previous studies show discrepancies concerning the effects of pretraining on spatial learning deficits induced by blockade of the N-methyl-d-aspartate (NMDA) receptor. These inconsistencies might be attributed to the differences in the nature of the pretraining tasks and the method of blocking NMDA receptors. In the present study, the authors pretrained rats in a spatial water maze task. The authors then trained them with a novel spatial task in a novel environment under chronic blockade of hippocampal NMDA receptors by intrahippocampal infusion of 2-amino-5-phosphonopentanoic acid (AP5) using osmotic pumps. Although the rats had acquired the basic techniques needed to solve a water-maze spatial task during pretraining, those given high or low doses of AP5 showed acquisition deficits. As the spatial pretraining failed to ameliorate the acquisition deficits of a new task in a novel environment, it was suggested that NMDA receptors were necessary in forming spatial representations. Because neither dose of AP5 affected the performance of a spatial task in the retention phase, sensory motor disturbances could not have caused these deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairments in negative patterning, but not simple discrimination learning, in rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis.

Rats with 192 IgG-saporin lesions of the nucleus basalis magnocellularis (NBM) and sham-operated rats were trained in either a simple discrimination paradigm assessing simple association learning or a negative patterning paradigm assessing configural association learning. In the simple discrimination task, rats were reinforced for responding to a light but were not reinforced for responding to a tone. In the negative patterning discrimination task, rats were reinforced for responding to either a light or a tone presented alone but were not reinforced for responding to both stimuli presented simultaneously. Simple discrimination learning was not affected, whereas acquisition of negative patterning was impaired by NBM lesions. Impaired configural association learning may reflect a loss in the ability of rats with NBM lesions to attend to multiple sensory stimuli or to cope with conflicting response strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disconnection of the amygdala central nucleus and substantia innominata/nucleus basalis disrupts increments in conditioned stimulus processing in rats.

Rats with a neurotoxic lesion of the amygdala central nucleus (CN) in one hemisphere and a 192 immunoglobulin G (192IgG)-saporin lesion of cholinergic neurons in the contralateral substantia innominata/nucleus basalis (SI/nBM) failed to show the enhanced attentional processing of a conditioned stimulus (CS) observed in sham-operated rats when that CS's predictive value was altered. Performance of these asymmetrically lesioned rats was poorer than that of rats with a unilateral lesion of either structure or with a symmetrical lesion of both structures in the same hemisphere. These results implicate connections between the CN and SI/nBM in the incremental attentional processing of CSs, extending previous research that has shown similar effects of bilateral lesions of either the CN or the SI/nBM. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The neurosteroid pregnenolone sulfate infused into the nucleus basalis increases both acetylcholine release in the frontal cortex or amygdala and spatial memory

GTP:AMP phosphotransferase (adenylate kinase isozyme 3, AK3) mutants were obtained by using the ability of AK3 to complement a temperature-sensitive mutation of Escherichia coli adenylate kinase (AKe). Five mutants, P16L, G19S, G91D, G91S, and P93L, had mutation sites located at two loops that are involved in substrate binding of the enzyme. P16L and G19S bearing changes at the first loop showed reduced affinity for both GTP and AMP, the extent of reduction being slightly higher for GTP than AMP. In contrast, G91S and P93L having alterations at the second loop had lower affinities for AMP. Only the alterations at the second loop strongly influenced the Vmax value of the enzyme. Another mutant, D163N, had a substitution at the site forming a salt bridge in adenylate kinase isozyme 1 (AK1), which influenced the Vmax as well as the Km values for both substrates. The kinetic characteristics of these mutants were comparable to those of the corresponding AK1 or AKe mutants. Furthermore, from the results of mutations T201P and T201A that had alterations in all the kinetic parameters of AK3 and from a comparison with the structure and the kinetic parameters of AKe, we expect that a residue(s) around Thr201 is involved in recognition of the base of nucleoside triphosphate.     

Nitric oxide is involved in the formation of learning and memory in rats: studies using passive avoidance response and Morris water maze task

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml).     

Tenoxicam does not enhance the spread of sensory block produced by intrathecal lidocaine

A chemically synthesized human pro-urokinase (pro-UK) CDNA was cloned into the expression vector PET-11d and expressed in E. coli BL21(DE3) pLysS under the control of the T7 promoter. Using 0.1 mmol/L IPTG induction, the expression level of the recombinant pro-UK attained up to 15% of the total bacterial proteins and existed as inclusion bodies. After denaturation and renaturation in vitro, the expressed pro-UK was purified to be identified by Zn2+ selective precipitation, immuno-affinity chromatography, and benzamidine affinity adsorption. The specific activity of the purified human pro-UK was about 110,000 IU/mg.     

MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced by pyrithiamine-induced encephalopathy in rats.

Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and assigned by block randomization to 1 of 4 treatments: pyrithiamine-induced thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days, control with MK-801 treatment, and control without MK-801. After 15 days of treatment followed by 21 days of recovery, the PTD rats showed significant deficits for DNMTS accuracy at retention intervals (RIs) that ranged from 3.0 sec to 15.0 sec, the RIs that produced 75% accuracy on DNMTS in staircase training, and the rate at which a novel radial arm maze task was learned. The PTD-treated rats had consistent lesions in the thalamus and the mammillary bodies. MK-801 protected rats from both behavioral deficits and brain lesions (assessed quantitatively and qualitatively) that were produced by the PTD treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of cerebral protein synthesis does not prolong short-term memory.

In 4 experiments, male Swiss-Webster CD-1 mice were given a single sc injection of a cerebral protein synthesis inhibitor, anisomycin (ANI, 1 mg/S), 20 min prior to a single trial of passive avoidance training. Ss demonstrated impaired retention at test given 3 hrs, 6 hrs, 1 day, and 7 days after training. Retention was not significantly different from that of saline controls when tests were given .5 or 1.5 hrs after training. Prolonging inhibition of brain protein synthesis by giving either 1 or 2 additional injections of ANI at 2 hrs or at 2 and 4 hrs after training did not prolong good retention performance. The temporal development of impaired retention in ANI-treated Ss could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory, these results indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is independent of protein synthesis and that the establishment of long-term memory depends on protein synthesis during or shortly after training. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective lesions of the nucleus basalis magnocellularis impair cognitive flexibility.

The authors tested the hypothesis that the cholinergic nucleus basalis magnocellularis (NBM) is involved in solving problems requiring cognitive flexibility. Rats with 192 IgG-saporin lesions of the NBM were assessed for perseveration (i.e., cognitive inflexibility) in the serial reversal of an operant discrimination and during subsequent extinction testing. It was hypothesized that the NBM lesion and control groups would not differ in the acquisition of the initial, simple discrimination, because this task does not demand cognitive flexibility. In contrast, it was hypothesized that the NBM lesion group would show perseveration during serial reversal and extinction testing. Results generally supported these hypotheses, suggesting that the NBM plays an important role in mediating cognitive flexibility. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Phencyclidine injections into the dorsal hippocampus disrupt long- but not short-term memory within a spatial learning task

Since the hippocampus is likely to be a major site of phencyclidine (PCP) action, the effects of various doses of PCP (1.8, 18 or 36 nM) as well as 3.6 nM MK-801 or saline injected directly into the dentate gyrus of the hippocampus was tested for acquisition of a spatial navigation task (dry land version of a water maze) using a paradigm that assesses short term memory based on learning within a day and long term memory based on learning between days. Results indicated that relative to saline or 1.8 nM PCP injected rats, rats with 18 or 36 nM PCP or 3.6 nM MK-801 injections were impaired in acquisition of the task as measured by increased distances traveled to find the food location between days but not within days. In additional experiments 36 nM PCP or 3.6 nM MK-801 did not produce any deficits in the acquisition of an object discrimination task. It is suggested that PCP through its blocking action of the NMDA receptor in the dentate gyrus or CA1 region of the dorsal hippocampus mediates the consolidation of new spatial location information.     

Effects of lesions of the nucleus basalis magnocellularis on the acquisition of cocaine self-administration in rats

The nucleus basalis magnocellularis (NBM) is one element in the limbic cortical-ventral striatal circuitry that has been implicated in reinforcement processes. The present study examined the involvement of the cholinergic neurons of the NBM in mediating aspects of cocaine reinforcement. Lesions of the NBM were made by injecting 0.01 M AMPA into the subpallidal basal forebrain. Following 4 days' recovery, rats were implanted chronically with catheters in the jugular vein. In three separate experiments, rats were trained to acquire cocaine self-administration under a FR1 schedule of reinforcement at doses of 0.25, 0.083 and 0.028 mg/injection. A dose-effect function was also determined at the end of the acquisition experiments using five different doses of cocaine (0.009, 0.028, 0.083, 0.25, 0.50 mg/injection) and saline which were presented once daily in a Latin square design. There were no significant differences between groups in the acquisition of cocaine self-administration at any of the three doses studied (0.028, 0.083 and 0.25 mg/injection), although at the lowest dose, lesioned animals responded at greater levels on both active and inactive levers. However, a shift to the left in the cocaine dose-response function was observed revealing that the lesioned group self-administered significantly higher amounts of low doses of cocaine than control rats. These data suggest that the integrity of the NBM is not a critical determinant of the reinforcing effects of cocaine during the acquisition of self-administration of the drug, but that NBM-dependent cholinergic mechanisms may nevertheless interact with the neural substrates mediating the reinforcing properties of cocaine. The data are relevant to recent hypotheses of functional interactions between the dopaminergic system and the cholinergic NBM.