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)     

Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.

Previous findings indicate that the memory-impairing effects of posttraining amygdala lesions are attenuated by increasing the number of training trials given prior to the induction of the lesion. The aim of this experiment was to determine whether the degree of impairment is also influenced by the footshock intensity used during training. Rats were given 1 trial of inhibitory avoidance (IA) training with either no footshock or a footshock at 1 of 3 intensities. Sham or neurotoxic amygdala lesions were induced 1 week later. On a retention test performed 4 days after surgery, the performance of all amygdala-lesioned rats given footshock training, including those given the lowest training footshock, was better than that of amygdala-lesioned rats given no training footshock. These findings of preserved retention of IA learning in rats given posttraining amygdala lesions do not support a general hypothesis that the amygdala is a locus of permanent changes underlying aversively motivated learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Pre- and posttraining infusion of N-methyl-D-aspartate receptor antagonists into the amygdala impair memory in an inhibitory avoidance task

Involvement of amygdaloid N-methyl-D-aspartate (NMDA) receptors in memory processes was investigated. Rats with cannulas implanted in the basolateral amygdala were trained on a 1 trial step-through inhibitory avoidance task and tested for 24-hr retention. Pretraining infusion of 2-amino-5-phosphonovaleric acid (APV) into the amygdala, but not striatum or hippocampus, produced a dose-dependent retention deficit, which was attenuated by immediate posttraining intra-amygdala infusion of NMDA. Posttraining APV infusion also caused a dose- and time-dependent retention deficit. Pretest APV infusion had no effect on performance in the retention test. Further, pre- or posttraining infusion of 5.0 micrograms APV failed to affect acquisition and retention in the Morris water maze task. These findings suggest that amygdala NMDA receptors are normally activated by aversive training and play a critical role in memory formation for affective experience.     

Comparative learning and memory deficits following hippocampal and caudate lesions in mice.

Examined the effects of hippocampal, caudate, combined hippocampal-caudate, and sham lesions on the passive avoidance and active escape performances of groups of female CF1 mice. Bilateral hippocampal or caudate lesions produced similar impairments of passive-avoidance retention 1 day after training in Ss operated upon 1 day prior to training. Hippocampal and caudate lesions similarly facilitated active-escape retention. When surgery was performed immediately after training, hippocampal or caudate lesions each impaired both passive-avoidance and active-escape retention 1 day later; no retention deficits were observed when surgery was performed 1 hr. after training. When surgery was performed immediately after training and passive-avoidance retest was conducted 1 hr. later, only hippocampal lesions impaired retention. These and other data suggest the mediation of different neuroanatomical substrates for short- and long-term memory and different processes for storage and forgetting. (19 ref.) (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)     

Differential effects of pretraining inactivation of the right or left amygdala on retention of inhibitory avoidance training.

Rats with bilateral cannulas aimed at the amygdalae received bilateral infusions of either buffer or lidocaine hydrochloride, or unilateral infusions of each, 5 min before continuous multiple-trial inhibitory avoidance (CMIA) training. Retention was tested 48 hr later. Some of the rats were retrained at this time and tested again 48 hr later. Bilateral infusions of lidocaine prior to the initial training impaired acquisition, retention, and relearning of the CMIA task. Unilateral infusions of lidocaine into the right or left amygdala did not affect acquisition. Rats given lidocaine into the right amygdala were impaired on retention 48 hr later. The findings are consistent with others indicating involvement of the amygdalae in acquisition and consolidation of aversively motivated learning and suggest possible differential involvement of the right and left amygdalae in memory consolidation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolonged suppression of human immunodeficiency virus type 1 (HIV-1) viremia in persons with advanced disease results in enhancement of CD4 T cell reactivity to microbial antigens but not to HIV-1 antigens

In rats, the septo-hippocampal system is important for memory encoding. Previous reports indicate that muscimol, a specific GABAergic agonist induces learning and memory deficits when infused into the medial septal area. The basolateral nucleus of the amygdala (BLA) modulates memory encoding in other brain areas, including the hippocampus. To explore the interactions between the septo-hippocampal system and amygdala in memory, we studied the effects of intra-medial septal infusions of muscimol in rats with BLA lesions. Animals received sham surgery or excitotoxic BLA lesions and were given infusions of either vehicle or muscimol (5 nmol) into the medial septal area 5 min prior to training sessions in inhibitory avoidance and water maze tasks. In the inhibitory avoidance task, muscimol-induced memory impairment was potentiated by BLA amygdala lesions. Additionally, in the water maze task, BLA-lesioned rats given muscimol infusions into the medial septal also showed memory impairment. These findings indicate that the MSA interacts with the BLA in the processing of memory storage.     

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

It is well known that lesions of the hippocampal formation produce a temporally graded retrograde amnesia for certain types of memory. A similar pattern of results has been reported with amygdaloid lesions in avoidance learning (K. C. Liang et al, 1982). The present study examined the effects of posttraining amygdaloid lesions using a Pavlovian conditioning task, fear-potentiated startle, in which the amplitude of the acoustic startle reflex is increased when elicited in the presence of a cue (e.g., a light) previously paired with footshock. Electrolytic lesions of the amygdala given either 6 or 30 days after training blocked the expression of potentiated startle, indicating no temporal gradient of amnesia over these intervals in this test paradigm. The effects of amygdaloid lesions on different measures of aversive learning are discussed. (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)     

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.     

Lack of a temporal gradient of retrograde amnesia following NMDA-induced lesions of the basolateral anygdala assessed with the fear-potentiated startle paradigm.

M. Kim and M. Davis (see record 1994-28571-001) previously reported that electrolytic lesions of the central nucleus of the amygdala, made 6 or 30 days after training, complctcly blockcd the expression of fear potentiated startle in rats. The present study shows that excitotoxic lesions of the basolateral amygdala also block fear-potentiated startle and do so whether the lesions are made soon (i.e., 6 days) or long (i.e., 30 days) after training. The relevance of these findings to various theories of amygdala function is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning.

This study examined the role of the amygdala in mediating the effects of glucocorticoids on spatial memory in rats. Adrenalectomy (ADX) induced 4–5 days prior to training impaired memory in a water-maze spatial task. This effect was reversed by a posttraining injection of dexamethasone (0.3 mg/kg sc) but not by corticosterone (0.3 mg/kg). Lesions of the basolateral (BLA), but not the central (CEA) or the medial (MEA), amygdala blocked the effects of ADX and dexamethasone. ADX also impaired acquisition. CEA, MEA, and BLA lesions blocked the ADX effect on acquisition. In adrenally intact rats, intracerebroventricular posttraining injections of a specific glucocorticoid receptor (GR or Type-ll) antagonist impaired retention, and BLA lesions blocked the effect of the GR antagonist. These findings provide evidence that the BLA is involved in mediating glucocorticoid influences on learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory

The effects of the NMDA receptor antagonist AP5, the nitric oxide synthase (NO) inhibitor NO-arg or the protein kinase A (PKA) inhibitor KT5720 on memory were evaluated. Rats bilaterally implanted in the CA1 region of the dorsal hippocampus were trained and tested in a step-down inhibitory avoidance task, and rats unilaterally implanted in the left posteroventral region of the caudate nucleus were trained and tested in a cued water maze task. Previous findings from this and other laboratories had found that lesions or pharmacological treatments of these sites significantly altered memory of these two tasks. Immediately after training, animals received intrahippocampal or intracaudate 0.5 microliter microinfusions of saline, AP5, NO-arg or KT5720. All three drugs impaired retention of inhibitory avoidance, but did not affect retention of the cued water maze. The findings suggest that NMDA receptor-, NO- and PKA-mediated processes in the dorsal hippocampus, but not in the caudate nucleus, are involved in memory.     

Novel experience prior to training attenuates the amnestic effects of posttraining ECS.

In this article, mice were given a novel exploratory experience 1 hr prior to training on a one-trial inhibitory avoidance task or a Y-maze shock-motivated visual discrimination task. Half of the animals in each group received immediate posttraining electroconvulsive shock (ECS) delivered through implanted cortical screws. Retention was tested 24 hr later. In the inhibitory avoidance task, retention was assessed by the response latencies on Day 2. In the Y-maze, the discrimination was reversed on Day 2 and retention of the original discrimination was assessed by errors made on six reversal training trials. Comparable results were obtained in the two tasks: ECS impaired retention in controls not given the novel experience but did not affect retention in mice given the novel experience. These findings are interpreted in terms of previous evidence, which suggests that ECS-induced amnesia may be mediated by the release of brain β-endorphin. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of amount of original training upon onset of a 24-hour memory capacity in neonatal mice.

Administered 0, 10, 25, or 40 trials in a shock-escape straight alley to 128 Swiss-Webster mice (Mus musculus) when 7 or 9 days old. All groups received an additional 25 training trials 24 hrs later. During original training, both age groups improved escape performance as a function of number of training trials. However, during retention testing, only the Ss trained when 9 days old displayed differences in performance due to amount of original training. Results support earlier research suggesting that the capacity for 24-hr retention of the escape response develops between 7 and 9 days of age in mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions of amygdala lesions with effects of pilocarpine and d-amphetamine on mouse killing, feeding, and drinking in rats

Repeated injections of 7.5 mg/kg pilocarpine induced mouse killing in both amygdala-lesioned and sham-operated rats, but more injections were required in the lesioned animals. Killing was evoked least readily in rats that showed substantial weight loss after surgery and that had damage to more medial regions of the amygdala. d-Amphetamine (.75, 1.50, or 3.00 mg/kg), administered either before or after a killing test, inhibited pilocarpine-induced killing in both surgical groups. Amygdala lesions attenuated pilocarpine-facilitated drinking in sated animals but did not alter the inhibitory effects of either pilocarpine or d-amphetamine on feeding or drinking.     

Lack of task specificity and absence of posttraining effects of atropine on learning.

Three experiments, with 91 male Lister rats, examined the effect of the cholinergic antagonist atropine on the acquisition of learning tasks known to be sensitive or insensitive to impairment by hippocampal lesions, on the retention of performance acquired in the absence of the drug, and on memory consolidation immediately after daily training trials. In Exp I, intraperitoneal atropine sulfate (10 or 50 mg/kg) injected 30 min prior to training severely impaired learning of both spatial and nonspatial discrimination tasks when compared with saline or atropine methylnitrate (50 mg/kg). In Exp II, atropine sulfate (50 mg/kg) also impaired spatial discrimination accuracy in Ss previously trained to asymptote under drug-free conditions. These deficits were not due to either peripheral drug effects of gross sensorimotor impairments. In Exp III, daily posttraining injections of atropine sulfate (50 mg/kg) failed to influence either learning or subsequent retention of place navigation in Ss trained to find a single hidden escape platform. The data confirm that profound learning deficits occur when training is conducted under atropine but offer no support to the hypotheses that cholinergic neurons play an important role in memory consolidation or other posttraining processes. Results demonstrate dissimilarities between the behavioral impairments induced by cholinergic blockade and hippocampal lesions under appropriate test regimes. (50 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraventricular galanin modulates a 5-HT1A receptor-mediated behavioural response in the rat

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.     

4-OH amphetamine enhances retention of an active avoidance response in rats and decreases regional brain concentrations of norepinephrine and dopamine.

In Exp I, an .82 mg/kg dose of 4-OH amphetamine hydrobromide (AMP) administered ip immediately following training in a 1-way active avoidance task enhanced retention performance of male ARS Sprague-Dawley rats measured 24 hrs later. In contrast, AMP in a dose range of .41–2.64 mg/kg, ip, did not affect retention of a swim escape task (Exp II). The behaviorally active dose of .82 mg/kg decreased dopamine concentrations in the amygdala and hippocampus. A dose of 8.2 mg/kg administered ip to naive untrained Ss (Exp III) decreased concentrations of norepinephrine measured in the amygdala, cortex, hippocampus, hypothalamus, and midbrain; decreased concentrations of dopamine in the amygdala, cortex, hippocampus, and striatum; and significantly reduced concentrations of norepinephrine and epinephrine in the adrenal medulla. In addition, because the integrity of the adrenal medulla is necessary for the enhancing action of AMP and because AMP reduces concentrations of catecholamines in the brain and adrenal medulla, it is possible that this drug affects retention performance by a dual action on the brain and the adrenal medulla. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)