Drugs acting upon the cyclic adenosine monophosphate/protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 micrograms/side), SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine ClH (0.3 microgram/side), timolol ClH (0.3 microgram/side), 8-HO-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side) or KT5720 (0.5 microgram/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT1A receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D1, beta, and 5HT1A receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.     

Intra-hippocampal estradiol infusion enhances memory in ovariectomized rats

Ovariectomized adult Long-Evans rats received an eight-trial training session in a hippocampal-dependent hidden platform water maze task. Following trial 8, rats received an intra-hippocampal injection of estradiol in a water soluble cyclodextrin inclusion complex (1.0, 2.0 or 5.0 micrograms/0.5 microliter), or saline. Twenty-four hours later, the retention test escape latencies of rats administered post-training intra-hippocampal injections of estradiol (5.0 micrograms) were significantly lower than those of saline treated rats, indicating a memory-enhancing effect of estradiol. Injections of estradiol (5.0 micrograms) given 2 h post-training had no effect on retention, indicating a time-dependent effect of estradiol on memory storage processes.     

Factors affecting the efficiency of peripheral blood stem cell collection in children treated with chemotherapy and G-CSF

Post-training administration of morphine (0.25, 0.5, or 1 mg/kg) dose-dependently impairs retention of an inhibitory avoidance response in mice. The effects on retention performance induced by the drug appear to be due to an effect on memory consolidation. In fact, they were observed when drugs were given at short, but not long, periods of time after training, i.e., when the memory trace was susceptible to modulation. Moreover, these effects are not to be ascribed to an aversive or a rewarding or nonspecific action of the drugs on retention performance, because the latencies during the retention test of those mice that had not received a footshock during the training were not affected by post-training drug administration. Pretreatment with either selective D1 or D2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride administered at per se noneffective doses (0.025 and 6 mg/kg, respectively) potentiated the effects of morphine, while either selective D1 or D2 receptor agonists SKF 38393 and LY 171555 at per se noneffective doses (5 and 0.25 mg/kg, respectively) antagonized the effects of the opiate on memory consolidation. No significant differences were evident between the effects of D1 and D2 receptor active compounds, thus suggesting that D1 and D2 receptor types are similarly involved in the effects of morphine on memory consolidation, in agreement with previously reported results. These results are discussed in terms of a possible inverse relationship of endogenous opioid and DA systems in the brain that are involved in memory processes.     

Apolipoprotein E antibodies affect the retention of passive avoidance memory in the chick

Isoforms of apolipoprotein E (ApoE) have been implicated as risk factors in Alzheimer's disease. We have, therefore, examined the possible role of ApoE in memory formation, using a one-trial passive avoidance task in day-old chicks. Birds were trained on the task and then at various times pre or post-training were injected intracerebrally with anti-ApoE. Immunofluorescence staining demonstrated the presence of the antibody bound to the neuropil, close to the injection site and adjacent to the ventricle, with a residence time in the brain of up to 30 min. Chicks that were injected 30 min pre-training or just post-training with 5 micrograms/hemisphere of the antibody learned the task, but were amnesic when tested at 30 min or at subsequent times up to 24 hr post-training. When tested at 24 hr, birds injected 5.5 hr post-training showed unimpaired retention. Birds injected with 5 micrograms/hemisphere of anti-ApoA-I (which has a brain distribution similar to that of anti-ApoE) at 30 min pretraining showed no amnesia, indicating the specificity of the effect to the ApoE. Possible mechanisms for this effect are discussed.     

Increased training in an aversively motivated task attenuates the memory-impairing effects of posttraining N-methyl-D-aspartate-induced amygdala lesions.

Examined the effect of variations in the amount of preoperative training on the retention deficit produced by posttraining lesions of the amygdaloid complex (AC). Rats received 1, 10, or 20 training trials in a footshock-motivated retention escape task 7 days before receiving N-methyl-{d}-aspartate (NMDA) lesions of the AC. Inhibitory avoidance retention performance, which was measured 4 days postoperatively, indicated that increased training improved retention in AC-lesioned animals as well as in control animals. The retention performance of AC-lesioned animals was impaired when compared with that of controls; however, the impairment was partially attenuated by increased preoperative training. The finding that AC-lesioned animals displayed greater locomotor activity on the retention test compared with nonlesioned controls suggests that the increased activity may have contributed to the impaired inhibitory avoidance retention performance. Two days after the retention test, some of the AC-lesioned animals were subsequently trained on a continuous multiple-trial inhibitory avoidance response in the same apparatus. AC lesions did not block acquisition or retention of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Treadmill performance of mice with cerebellar lesions: 1. Purkinje cell degeneration mutant mice

The purpose of this study was to evaluate the sensorimotor skills of a spontaneous mouse mutant, Purkinje cell degeneration (PCD), marked by selective cerebellar cortical atrophy on a treadmill activated at 1 of 2 speeds and at 1 of 3 slopes, requiring forward movements to avoid footshocks. There was no difference in latencies before falling from the belt between PCD mutants and controls during acquisition. However, PCD mutants were impaired on the fast treadmill during retention, implicating the cerebellum in the memory of a motor skill. During acquisition of the slow treadmill task at the 2 lowest slopes of inclination, PCD mutants spent more time walking than controls, an indication of a decreased ability of coordinating whole body movements. The same pattern of higher walking time on the slow treadmill in PCD mutants was evident during retention. These results indicate that the cerebellar cortex is involved in the acquisition and the retention of a task requiring equilibrium.     

Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet

Recent studies suggest a role of the neural cell adhesion molecules L1 and NCAM in mechanisms of memory storage. In the present study we analyzed the effect of continuous intraventricular infusion of polyclonal antibodies directed against L1 (antiL1) or NCAM (antiNCAM) on the performance of male Wistar rats during the acquisition and retention of a spatial learning task (Morris water-maze). In this task animals have to learn the spatial position of a hidden escape platform in a water tank to escape onto it. During acquisition of the task animals with continuous infusion of antiNCAM - but not those infused with antiL1 - showed day-dependent attenuated learning in comparison to controls (P = 0.001). Control animals were either injected with vehicle (PBS) or with polyclonal antibodies raised against liver cell membrane. When the escape platform was removed during the retention test (transfer test), the performance of animals continuously infused with antiL1 as well as those continuously infused with antiNCAM showed an impaired search pattern when compared with the performance of control animals (P = 0.001 and 0.04, respectively). Whereas control animals spent up to 46% of their time searching for the platform in the correct quadrant, the time antiL1- and antiNCAM-infused animals spent in this quadrant was closer to chance level (30.5% and 36.5%), respectively). The present data provide additional support for an involvement of the two adhesion molecules L1 and NCAM in synaptic plasticity underlying memory storage.     

Persistence of quinalphos and occurrence of its primary metabolite in soils

PURPOSE: This study focuses on the quantification of genetic and environmental factors in arm strength after high-resistance strength training. METHODS: Male monozygotic (MZ, N = 25) and dizygotic (DZ, N = 16) twins (22.4 +/- 3.7 yr) participated in a 10-wk resistance training program for the elbow flexors. The evidence for genotype*training interaction, or association of interindividual differences in training effects with the genotype, was tested by a two-way ANOVA in the MZ twins and using a bivariate model-fitting approach on pre- and post-training phenotypes in MZ and DZ twins. One repetition maximum (1RM), isometric strength, and concentric and eccentric moments in 110 degree arm flexion at velocities of 30 degrees x s(-1), 60 degrees x s(-1), and 12 degrees x s(-1) were evaluated as well as arm muscle cross-sectional area (MCSA). RESULTS: Results indicated significant positive training effects for all measures except for maximal eccentric moments. Evidence for genotype*training interaction was found for 1RM and isometric strength, with MZ intra-pair correlations of 0.46 and 0.30, respectively. Bivariate model-fitting indicated that about 20% of the variation in post-training 1RM, isometric strength, and concentric moment at 120 degrees x s(-1) was explained by training-specific genetic factors that were independent from genetic factors that explained variation in the pretraining phenotype (30-77%). CONCLUSIONS: Genetic correlations between measures of pre- and post-training strength were indicative for high pleiotropic gene action and minor activation of training-specific genes during training.     

Retention impairment by posttraining epinephrine: Role of state dependency and of endogenous opioid mechanisms.

Mice were trained in a step-through inhibitory avoidance task with a 0.6-mA, 60-Hz, 2-s footshock and were tested for retention 3 or 6 hr later. Posttraining intraperitioneal administration of a high dose (25.0 μg per mouse) of epinephrine (Epi) impaired retention; this effect was counteracted by another injection of the same dose of Epi given before retention testing either 3 or 6 hr after training. When administered before the 6-hr test but not the 3-hr test, however, Epi enhanced retention (i.e., above that of controls). The retention enhancement, but not the reversal of impairing effects of posttraining Epi, was antagonized by naltrexone (20.0 μg per mouse). Naltrexone, when administered alone, had no effect on retention when given before testing. However, posttraining administration of naltrexone produced an enhancement of retention detectable 6 but not 3 hr after training. Furthermore, posttraining naltrexone also blocked the impairing effect of posttraining Epi otherwise seen 6 hr after training. Results suggest that the impairment of retention caused by posttraining Epi is attributable to the induction of state dependency based on an Epi state. When the animals are tested 3 hr after training, this effect appears alone. But, when tested 6 hr after training, the Epi effect appears together with an opioid presumably β-endorphin-mediated, state dependency. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Current clinical issues in the management of herpes simplex virus infections in patients with HIV

The effect of the Ca2+ blocker verapamil on amnesia induced by electroconvulsive shock (ECS) or by the alpha-adrenoceptor agonist clonidine was studied in male Wistar rats trained in passive avoidance task ("step down"). Clonidine (0.1 mg/kg, i.p.) and ECS induced a pronounced amnesia, significantly reducing the percentage of rats that had acquired the task upon retention tests, given 3 h, 24 h and 7 days after training. Verapamil (10 mg/kg) administered orally for 12 days (5 days before and 7 days after training) completely abolished the ECS- or clonidine-induced amnesia. These data suggest that calcium channel blocker verapamil has a protective effect against experimentally provoked memory deficit and might be useful for the treatment of cognitive disorders.     

Stria terminalis lesions attenuate the effects of posttraining naloxone and beta-endorphin on retention.

These experiments examined the effect of posttraining administration of naloxone and β-endorphin in rats with lesions of the stria terminalis (ST). Rats with sham or bilateral ST lesions were trained either in an inhibitory avoidance task or in a Y-maze discrimination task and, immediately after training, received an ip injection of saline, naloxone (0.5, 2.0, or 5.0 mg/kg in the avoidance task; 3.0 mg/kg in the Y-maze task), or β-endorphin (10.0 μg/kg). Retention of each task was tested 24 hrs following training. In the Y-maze task, retention was assessed by training on a reversed discrimination. The ST lesions did not affect retention of either task in otherwise untreated animals. However, in both tasks, ST lesions attenuated the memory-enhancing effects of naloxone as well as the memory-impairing effects of β-endorphin. These findings are consistent with other recent evidence suggesting that the amygdala may be involved in posttraining memory modulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of a reminder cue on amnesia induced by stimulation of amygdala and hippocampus.

Examined the effects of a footshock reminder (FSR) in restoring memory after discrete electrical brain stimulation in 119 male Long-Evans rats. Ss received low-level bilateral electrical stimulation of either the amygdala or the hippocampus after training in a 1-trial passive avoidance task. Ss receiving stimulation showed amnesia when tested 24 hrs after training. One hour after the retention test, Ss received an FSR. 23 hrs later in a 2nd retention test, hippocampus-stimulated Ss showed recovery of memory, while amygdala-stimulated Ss did not. Stimulated Ss that did not receive an FSR remained amnesic. In addition, the effects of amygdala and hippocampal stimulation applied after the FSR were examined. On the 2nd retention test, amygdala stimulation disrupted the FSR effect, while hippocampal stimulation had no deleterious effects. Data are interpreted from a memory-attribute point of view that suggests that the amygdala and hippocampus may be differentially involved in the processing of particular attributes of the learning task. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory of rats with amygdala lesions induced 30 days after footshock-motivated escape training reflects degree of original training.

This experiment was conducted to determine whether the amount of preoperative training influences the effects, on retention, of amygdala lesions induced 30 days after escape training. Rats received 1 or 10 footshock-motivated escape training trials; 30 days later, sham or neurotoxic amygdala lesions were induced. Results of an inhibitory avoidance test performed 4 days after surgery indicated that amygdala lesions impaired retention performance; however, increased preoperative training partially attenuated the retention deficit. Increased preoperative training also attenuated the impairing effects of the lesions on retention assessed in a continuous multiple-trial inhibitory avoidance task given 36 days after the original escape training. The finding that amygdala-lesioned rats remembered the escape training suggests that the amygdala is not a critical locus of the changes underlying the long-term retention of footshock-motivated escape training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Treadmill performance of mice with cerebellar lesions: 1. Purkinje cell degeneration mutant mice": Correction.

Reports an error in the original article by N. LeMarec and R. Lalonde (Behavioral Neuroscience, 1998[Feb], Vol 112[1], 225–232). On page 227, Figure 1 was printed incorrectly. (The following abstract of this article originally appeared in record 1997-38942-020.) The purpose of this study was to evaluate the sensorimotor skills of a spontaneous mouse mutant, Purkinje cell degeneration (PCD), marked by selective cerebellar cortical atrophy on a treadmill activated at 1 of 2 speeds and at 1 of 3 slopes, requiring forward movements to avoid footshocks. There was no difference in latencies before falling from the belt between PCD mutants and controls during acquisition. However, PCD mutants were impaired on the fast treadmill during retention, implicating the cerebellum in the memory of a motor skill. During acquisition of the slow treadmill task at the 2 lowest slopes of inclination, PCD mutants spent more time walking than controls, an indication of a decreased ability of coordinating whole body movements. The same pattern of higher walking time on the slow treadmill in PCD mutants was evident during retention. These results indicate that the cerebellar cortex is involved in the acquisition and the retention of a task requiring equilibrium. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats.

Rats were submitted to a training and a test session in a shuttle avoidance task. In some groups, a second training session was interpolated 2 or 24 hr after the first session. In others, a session of extinction was interpolated 2 or 24 hr after the training session. When the interpolated task was 2 hr after training, training-test interval was 24 hr. When the interpolated task was 24 hr after training, training-test interval was 48 hr. The additional training enhanced, and the extinction depressed, retention test performance. Diazepam, given 30 min prior to the first (or only) training session enhanced the performance of avoidance responses in that session but inhibited it in the subsequent retention test. Diazepam given 90 min after training had no effect on retention. Diazepam given 30 min prior to either the additional training session or the extinction session did not affect performance in that session but canceled their effects on retention test performance. The effects are related to the previously described prevention by diazepam of interfering effects on memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Limited period of action of testosterone on memory formation in the chick.

Domestic chicks will normally peck readily at small colored beads. However, a peck at a bead with an unpleasant taste usually results in a long-lasting aversion to beads of that type. The present study describes experiments in which pretraining and training were separated by a standard interval and then followed by retention tests at varying times in different groups of Warren sex-link chicks. The effect of variation in the interval between pretraining and training is also examined. Results show that if prior experience ("pretraining") of a bead of the type that is to be used in a later aversive training trial is given to testosterone-treated Ss, it interferes with the retention of avoidance. Interference by pretraining is effective only within sharply defined periods of time: when the pretraining–training interval is either less than 2 min (short-term) or greater than about 25 min (long-term). When pretraining and training are separated by 90 min or more, the steroid can be effective when injected up to 30 min after pretraining. It appears to change the character of the consolidating memory trace of pretraining in such a way as to make the consolidation of later, contradictory information from training less likely. The initial stage of this information is apparantly unaffected, since retention does not begin to decay until 30–60 min after training. Short-term interference leads to loss of avoidance within 5 min of training and can be used to demonstrate that the latency of action of the hormone in this task is less than 20 min following a sc injection. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A single pre-training glucose injection induces memory facilitation in rodents performing various tasks: contribution of acidic fibroblast growth factor

Effects of a pre-training intraperitoneal glucose injection on learning and memory were tested using two tasks: passive avoidance and Morris water maze. In the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h prior) to a trial that combined acquisition with passive avoidance of foot shock showed a significantly increased retention latency when tested 24 h later. Thus, this effect was time-dependent, and it was also found to be dose-dependent by further experiment. In contrast, 2-deoxy-D-glucose and fructose had no such effect. In the Morris water maze task, glucose injection 2 or 3 h before a block of trials enhanced the spatial memory performance of mice. These glucose-induced memory-facilitation effects were abolished by an intracerebroventricular injection of anti-acidic fibroblast growth factor antibody 30 min before the glucose injection, suggesting a critical role for endogenous acidic fibroblast growth factor in this facilitatory effect. Furthermore, continuous intracerebroventricular infusion of acidic fibroblast growth factor in rats significantly increased retention latency (when tested repeatedly on successive days using a passive avoidance task). Our earlier studies demonstrated that brain acidic fibroblast growth factor is produced in the ependymal cells of the cerebroventricular system, and is released into the cerebrospinal fluid following either a meal or a (intraperitoneal or intracerebroventricular) glucose injection. This released acidic fibroblast growth factor also diffuses into the brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus, and elsewhere in the brain some 2 h after the meal or glucose injection. These and the present findings indicate (i) that pre-training glucose injection improves memory performance, and (ii) that acidic fibroblast growth factor, especially by its action within the hippocampus, is involved in this enhancement process.     

Cholinergic mechanisms and alterations in behavioral suppression as factors producing time-dependent changes in avoidance performance.

Studied 360 male hooded and Holtzman rats that received either one-way or shuttle-avoidance training at 1 of 4 retention intervals following exposure to signaled inescapable shock. Hooded rats exhibited a -shaped retention function in both tasks, while Holtzman rats demonstrated a curvilinear function only in the shuttle task. In Exp. II scopolamine improved and physostigmine disrupted shuttle-avoidance performance, and both altered the form of the retention curve in 300 male Holtzman rats. In the 1-way task physostigmine essentially produced a curve which approximates a -shaped retention function early in training. The data support a hypothesis based on activity changes, subserved by adrenergic-cholinergic mechanisms, as being involved in the production of the Kamin effect. (42 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulation of specific regions of brain in rats modifies retention for newly acquired and old habits

Three experiments were designed to investigate some effects of low-level stimulation of the amygdaloid complex (AMYG) and the mesencephalic reticular formation (MRF). Experiment 1 used a tilt box to test for motivational and/or reinforcement effects and failed to demonstrate these effects with stimulation of either structure. Experiment 2 used a one-trial fear-conditioning task and revealed that stimulation of the AMYG disrupted retention when given immediately after training or, under some conditions, 4 days after training. In the same task, Experiment 3 showed that stimulation of the MRF enhanced retention when given immediately after training or, under some conditions, 4 days after training. These data indicate that under these conditions, modification of retention by low-level stimulation of specific brain structures is independent of the age of the memory. Some implications of this result are discussed.     

The cortical neuropeptide, cortistatin-14, impairs post-training memory processing

Cortistatin-14, a neuropeptide, is present primarily in the cortex and hippocampus. In the hippocampus, cortistatin-14 inhibits pyramidal cell firing and co-exists with GABA. To determine if cortistatin-14 would impair retention, saline or cortistatin-14 were injected intracerebroventricularly after footshock avoidance training in CD-1 mice. After 1 week, training was resumed to determine the effect of cortistatin-14 on retention. Cortistatin-14 was found to impair retention relative to the control group at doses of 0.5-5.0 micrograms.