Affect Retention Performance Research Articles

Open field exposure facilitates recovery from an aversive emotional event: Involvement of adrenergic and cholinergic transmitter systems

Successive negative contrast (SNC) is an incentive relativity procedure that has been widely used to model emotional reactivity in rodents. The reward downshift experienced during SNC is thought to result in frustration. The exploration of a novel open field (OF), a complex situation involving stress induction and novelty detection, can enhance or block the acquisition of associative and non-associative memories. Previous experiments found a modulatory effect of OF, applied before downshift trials, on SNC. This schedule, however, can affect retention performance by influencing attentional, motivational, motor or sensory-perceptual mechanisms at training or retention testing. The use of post-training OF exposure avoids these confounds. This work assessed the effect of OF exposure after the acquisition of the downshifted memory, with the goal of targeting the consolidation of this mnemonic trace. We also investigated the involvement of the cholinergic and adrenergic systems in this phenomenon. The results indicated that OF facilitates recovery from reward loss and that both transmitter systems, cholinergic and adrenergic, play a role in this effect of OF.

The Influence of Movement Initiation Deficits on the Quantification of Retention in Parkinson’s Disease

In patients with an impaired motor system, like Parkinson’s disease (PD), deficits in motor learning are expected and results of various studies seem to confirm these expectations. However, most studies in this regard are behaviorally based and quantify learning by performance changes between at least two points in time, e.g., baseline and retention. But, performance in a retention test is also dependent on other factors than learning. Especially in patients, the functional capacity of the control system might be altered unspecific to a certain task and learning episode. The aim of the study is to test whether characteristic temporal deficits exist in PD patients that affect retention performance. We tested the confounding effects of typical PD motor control deficits, here movement initiation deficits, on retention performance in the motor learning process. 12 PD patients and 16 healthy control participants practiced a virtual throwing task over 3 days with 24 h rest between sessions. Retention was tested comparing performance before rest with performance after rest. Movement initiation deficits were quantified by the timing of throwing release that should be affected by impairments in movement initiation. To scrutinize the influence of the initiation deficits on retention performance we gave participants a specific initiation intervention prior to practice on one of the three practice days. We found that only for the PD patients, post-rest performance as well as release timing was better with intervention as compared to without intervention. Their performance could be enhanced through a tuning of release initiation. Thus, we suggest that in PD patients, performance decline after rest that might be easily interpreted as learning deficits could rather result from disease-related deficiencies in motor control.

Bidirectional effects of benzodiazepine binding site ligands in the passive avoidance task: differential antagonism by flumazenil and β-CCt

Recent research on genetically modified mice has attributed the amnesic effect of benzodiazepines mainly to the α 1-containing GABA A receptor subtypes. The pharmacological approach, using subtype selective ligands, is needed to complement genetic studies. We tested the effects of the non-selective antagonist flumazenil (0–20.0 mg/kg), the preferential α 1-subunit selective antagonist β-carboline-3-carboxylate- t-butyl ester (β-CCt) (0–30.0 mg/kg), the non-selective agonist midazolam (0–2.0 mg/kg), the preferential α 1-subunit selective agonist zolpidem (0–3.0 mg/kg), and the non-selective inverse agonist methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) (0–2.0 mg/kg) in the one-trial step-through passive avoidance task in rats. The compounds were administered intraperitoneally, before the acquisition test. Flumazenil and β-CCt did not affect retention performance. Midazolam and zolpidem induced amnesia in a dose-dependent manner. The complete reversal of amnesia was unattainable. The effects of zolpidem were significantly attenuated by the both, flumazenil (10.0 mg/kg) and β-CCt (30.0 mg/kg); by contrast, only flumazenil was considerably effective when combined with midazolam. DMCM exerted promnesic effects at 0.2 mg/kg, in an inverted U-shape manner. Both antagonists tended to abolish this action. The results indicate that some other α-subunit(s), in addition to the α 1-subunit, contribute to the amnesic actions of non-selective benzodiazepine site agonists in the passive avoidance task. On the other hand, a significant part of the DMCM-induced promnesic effect could involve the α 1-subunit and/or other putative β-CCt-sensitive binding site(s).

Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala.

Previous findings indicate that administration of abeta-adrenoceptor antagonist systemically blocks glucocorticoid impairment of memory retrieval. Here, we report that beta-adrenoceptor activation in the hippocampus and the basolateral complex of the amygdala (BLA) is implicated in the impairing effects of glucocorticoids on memory retrieval. The specific glucocorticoid receptor (GR) agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362) (15 ng) infused into the hippocampus of male Sprague Dawley rats 60 min before water maze retention testing, 24 hr after training, impaired probe trial retention performance, as assessed by quadrant search time and initial latency to cross the platform location. Because we found previously that RU 28362 infused into the hippocampus does not affect water maze acquisition or immediate recall, the findings suggest that the GR agonist-induced retention impairment was attributable to a selective influence on long-term memory retrieval. Likewise, systemic injections of the beta1-adrenoceptor partial agonist xamoterol (3.0 or 10.0 mg/kg, s.c.) 60 min before the probe trial dose-dependently impaired retention performance. The beta-adrenoceptor antagonist propranolol (2.0 mg/kg) administered subcutaneously before retention testing did not affect retention performance alone, but blocked the memory retrieval impairment induced by concurrent intrahippocampal infusions of RU 28362. Pretest infusions of the beta1-adrenoceptor antagonist atenolol into either the hippocampus (1.25 microg in 0.5 microl) or the BLA (0.5 microg in 0.2 microl) also prevented the GR agonist-induced memory retrieval impairment. These findings suggest that glucocorticoids impair retrieval of long-term spatial memory by facilitating noradrenergic mechanisms in the hippocampus, and additionally, that norepinephrine-mediated BLA activity is critical in enabling hippocampal glucocorticoid effects on memory retrieval.

A systemically administered β-adrenoceptor antagonist blocks corticosterone-induced impairment of contextual memory retrieval in rats

Several studies have reported that glucocorticoids impair memory retrieval. The present study examined in male Sprague–Dawley rats the effects of systemically administered corticosterone on retrieval of memory for inhibitory avoidance training. Corticosterone (3.0 mg/kg, s.c.) injected 30 min before retention testing, 48 h after training, significantly impaired retention performance, as compared to vehicle treatment, of rats tested in the training context. In contrast, corticosterone administration did not impair retrieval when rats were tested for retention in a different context. Corticosterone did also not impair retention performance of rats given a mild-intensity footshock that resulted in only weak, non-contextual memory. These findings strongly suggest that corticosterone selectively impaired retrieval of contextual information associated with the training context. The centrally acting β-adrenoceptor antagonist propranolol (2.0 mg/kg), co-administered in a dose that did not affect retention performance alone, blocked the impairment in contextual memory retrieval induced by corticosterone. These findings provide evidence for the view that glucocorticoids interact with noradrenergic mechanisms in influencing memory retrieval.

Septal infusions of glucose or pyruvate, but not fructose, produce avoidance deficits when co-infused with the GABA agonist muscimol

Although glucose typically enhances memory or reverses memory deficits, glucose can also produce memory deficits when co-infused with the γ-aminobutyric acid (GABA) agonist muscimol into the medial septum ( Parent & Gold, 1997; Parent, Laurey, Wilkniss, & Gold, 1997). To date the mechanisms underlying the memory-impairing interaction between GABA and glucose remain unknown. Here we investigate whether this effect is the result of hyperosmolar conditions or may involve glucose metabolism. Male Sprague–Dawley rats were given one-trial inhibitory avoidance training after receiving septal infusions of vehicle (phosphate-buffered saline, 0.5 μl), the GABA A agonist muscimol (3 nmol), glucose (16.5, 33, or 66 nmol), fructose (33 nmol), pyruvate (33 nmol), or a solution containing muscimol combined with glucose, fructose, or pyruvate. Retention performance was tested 48 h later. Infusions of glucose, pyruvate, fructose, or muscimol alone did not affect retention performance. However, co-infusions of all doses of glucose (16.5, 33, or 66 nmol) or the glycolytic end product pyruvate with muscimol impaired retention performance. Co-infusions of fructose with muscimol did not affect retention performance. These results suggest that the memory-impairing interaction between glucose and muscimol does not result from hyperosmolar conditions, because equiosmolar concentrations of fructose do not mimic the effects of glucose and the memory deficits do not vary as a function of glucose concentration. The finding that pyruvate mimicked the effects of glucose and impaired memory when combined with muscimol suggests that glucose metabolism may be involved in the memory-impairing interaction between glucose and GABA A receptors in the medial septum.

Basolateral Amygdala–Nucleus Accumbens Interactions in Mediating Glucocorticoid Enhancement of Memory Consolidation

Systemic or intracerebral administration of glucocorticoids enhances memory consolidation in several tasks. Previously, we reported that these effects depend on an intact basolateral nucleus of the amygdala (BLA) and efferents from the BLA that run through the stria terminalis (ST). The BLA projects directly to the nucleus accumbens (NAc) via this ST pathway. The NAc also receives direct projections from the hippocampus and, therefore, may be a site of convergence of BLA and hippocampal influences in modulating memory consolidation. In support of this view, we found previously that lesions of either the NAc or the ST also block the memory-modulatory effect of systemically administered glucocorticoids. The present experiments examined the effects of lesions of the NAc or the ST on the memory-modulatory effects of intracerebral glucocorticoids on inhibitory avoidance training. Microinfusions of the specific glucocorticoid receptor agonist 11beta,17beta-dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 1.0 or 3.0 ng) into either the BLA or the hippocampus of male Sprague Dawley rats administered immediately after training enhanced the 48 hr retention performance in a dose-dependent manner. Bilateral lesions of the NAc or the ST alone did not affect retention performance but blocked the memory enhancement induced by intra-BLA or intrahippocampal glucocorticoid receptor agonist administration. These findings indicate that the BLA-NAc pathway plays an essential role in mediating glucocorticoid effects on memory consolidation and suggest that the BLA interacts with hippocampal effects on memory consolidation via this pathway.

Glucocorticoid receptor activation in the rat nucleus of the solitary tract facilitates memory consolidation: involvement of the basolateral amygdala.

These experiments examined the involvement of glucocorticoid receptors (GRs or type II) located in the A2-noradrenergic cell group of the rat nucleus of the solitary tract (NTS) in modulating memory storage. Bilateral intra-NTS infusions (0.5 microL) of the specific GR agonist RU 28362 (11beta, 17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one), in doses ranging from 0.01 to 10.0 ng, immediately after inhibitory avoidance training produced a dose-dependent enhancement of 48 h retention performance. Infusions of 0.1 or 1.0 ng of the agonist enhanced retention, whereas lower or higher doses were ineffective. Post-training infusions of the GR antagonist RU 38486 [17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(1-pr opynyl)-o estra-4,9-dien-3-one, 0.01-10.0 ng] into the NTS did not significantly affect retention performance, but shifted the dose-response effects of post-training systemic injections of the synthetic glucocorticoid dexamethasone to the right. These results indicate that activation of GRs in the NTS can influence memory formation for inhibitory avoidance training, and suggest that the effects of circulating glucocorticoids on memory are mediated, in part, by an activation of GRs in the NTS. Additionally, pretraining infusions of the beta1-adrenergic antagonist atenolol (0.5 microg in 0.2 microL) into the basolateral nucleus of the amygdala (BLA), a brain structure which receives noradrenergic projections from the NTS and is implicated in memory storage modulation, blocked the memory-enhancing effects of the GR agonist (1.0 ng) infused into the NTS. These findings provide evidence that memory storage is modulated by glucocorticoid binding to GRs in noradrenergic cell bodies in the NTS and suggest that these modulatory effects are conveyed by ascending projections to the BLA.

Strain-dependent involvement of D1 and D2 dopamine receptors in muscarinic cholinergic influences on memory storage

These experiments examined the interaction of muscarinic and dopaminergic systems in influencing memory for one-trial inhibitory avoidance training in mice of the C57BL/6 and DBA/2 strains. In both strains, immediate post-training systemic administration of the muscarinic cholinergic agonist oxotremorine enhanced retention and the cholinergic antagonist atropine impaired retention. No effects were seen with injections 2 h post-training. Furthermore, the drugs did not affect retention performance of animals that received no footshock on the training trial. These results confirm previous findings indicating that muscarinic cholinergic drugs affect memory by influencing memory consolidation. In C57 mice, pretreatment with selective D1 or D2 dopamine (DA) receptor agonists (SKF 38393 or LY 171555, respectively) in otherwise non-effective doses (5 and 0.25 mg/kg, respectively) potentiated the effects of oxotremorine (0.04 mg/kg). Furthermore, in C57 mice pretreatment with selective D1 or D2 receptor antagonists (SCH 23390 or (−)-sulpiride) in otherwise non-effective doses (0.025 and 6 mg/kg, respectively) blocked the memory enhancing effects of oxotremorine. The memory impairing effects of atropine (3 mg/kg) were blocked by the D1 and D2 selective agonists and potentiated by the selective D1 or D2 antagonists. In contrast, in DBA mice, the D1 and D2 selective agonists antagonised the memory enhancing effects of oxotremorine (0.02 mg/kg) and potentiated the effects of atropine (2 mg/kg). Furthermore, the D1 and D2 antagonists potentiated the effects of oxotremorine and antagonised those of atropine. These findings indicate that although muscarinic cholinergic influences on memory storage are comparable in mice of these two strains, the cholinergic-dopaminergic interactions are opposite in the two strains. These results have implications for hypotheses of cholinergic and dopaminergic regulation of memory storage.

Sulpiride infused into the nucleus accumbens posttraining impairs memory of spatial water maze training.

A variety of nucleus accumbens (NA) manipulations induce deficits in spatial learning and memory tasks. It is not known, however, if these deficits reflect influences on memory or on other processes affecting performance. The experiments in this article were undertaken to examine the involvement of the NA in memory consolidation in a spatial task. Rats were given 1 training session in a spatial water maze immediately followed by intra-NA infusions of sulpiride or saline vehicle. A probe test 2 days later revealed an impairing effect of sulpiride on several retention measures. Sulpiride infused into the NA either 2 hr posttraining in the spatial task or immediately posttraining in a cued water maze task did not affect retention performance. These findings suggest that the impairing effects of immediate posttraining sulpiride in the spatial task are due to interference with spatial water maze-specific consolidation processes involving the NA.

Effects of β-CCE on retention of aversively- and appetitively-motivated tasks in rats

Beta-carboline-3-carboxylic acid ethyl ester (β-CCE; 1.0 or 5.0 mg/kg, IP) or vehicle control was administered to male Sprague-Dawley rats immediately after training in an aversively- or appetitively-motivated task. Aversively-motivated training consisted of a one-trial step-through inhibitory (passive) avoidance task with a 0.6 mA, 1.0 s foot shock. Retention was tested 21 days after training. The 5.0 mg/kg dose of β-CCE significantly enhanced retention performance in the inhibitory avoidance task compared to the vehicle control. For appetitive training, the animals learned a T-maze for water reward. Retention was tested 48 h later, and neither dose of β-CCE was found to affect retention performance. These results suggest that β-CCE, when administered immediately after training, may alter retention performance of an aversively-motivated task but not an appetitive task.

Adrenocortical suppression blocks the memory-enhancing effects of amphetamine and epinephrine.

This study examined glucocorticoid-adrenergic interactions in modulating acquisition and memory storage for inhibitory avoidance training. Systemically (s.c.) administered amphetamine (1 mg/kg), but not epinephrine (0.1 mg/kg) or the peripherally acting amphetamine derivative 4-OH amphetamine (2 mg/kg), given to rats shortly before training facilitated acquisition performance in a continuous multiple-trial inhibitory avoidance (CMIA) task. Adrenocortical suppression with the 11beta-hydroxylase inhibitor metyrapone (50 mg/kg; s.c.), given to rats 90 min before training, did not block the effect of amphetamine and did not affect acquisition performance of otherwise untreated animals. Retention of CMIA and one-trial inhibitory avoidance was enhanced by either pre- or posttraining injections of amphetamine as well as 4-OH amphetamine and epinephrine. The finding that injections of amphetamine and epinephrine have comparable effects on memory is consistent with the view that amphetamine may modulate memory storage, at least in part, by inducing the release of epinephrine from the adrenal medulla. Metyrapone pretreatment blocked the memory-enhancing effects of amphetamine, 4-OH amphetamine, and epinephrine but did not affect retention performance of otherwise untreated animals. Posttraining injections of different doses of epinephrine (ranging from 0.0001 to 1.0 mg/kg) produced a dose-dependent memory enhancement for inhibitory avoidance training and metyrapone blocked the memory-enhancing effects of all these doses. These findings provide further evidence that the sympathoadrenal and adrenocortical systems are intimately coupled during processes of memory storage.

5,7-DHT—induced lesions of the nucleus basalis or frontal cortex do not block passive avoidance retention impairments produced by p-chloroamphetamine in rats

The effects of serotonergic lesions of the nucleus basalis of Meynert (nbM) or regions within the frontal cortex (FCTX) induced with 5,7-dihydroxytryptamine were examined to determine whether such damage would block the amnesia-producing effect of pretraining (30 min) p-chloroamphetamine (PCA; 2.5 mg/kg) in rats trained on passive avoidance. Results indicated that, irrespective of their lesion condition, all groups treated with PCA exhibited 72-h retention impairments. Serotonergic lesions of the nbM or FCTX alone did not affect retention performance despite producing extensive depletions of serotonin (34.8%–84.7%) and 5-hydroxyindoleacetic acid (59.0%–86.0%). Neither lesion procedure, nor the administration of PCA, had an effect on activity levels of cholinergic markers choline acetyltransferase and acetylcholinesterase within the frontal cortex. These data demonstrate that the memory-impairing effects of PCA are not (1) dependent on the existence of releasable pools of serotonin in the nbM or FCTX, (2) mediated by stimulation of serotonergic receptors in the nbM or FCTX, or (3) related to disruption of cholinergic activity within the frontal cortex. These data also reveal that serotonergic lesions to the nbM or FCTX by themselves do not produce impairments in retention on passive avoidance.

Posttraining infusion of lidocaine into the amygdala basolateral complex impairs retention of inhibitory avoidance training

The present experiment examined the role of the central nucleus and basolateral complex in the retention of inhibitory avoidance training by reversibly inactivating these regions with lidocaine immediately following training. Male Sprague-Dawley rats were surgically implanted bilaterally with cannulae aimed at the central nucleus or the basolateral complex. One week later, they received one trial inhibitory avoidance training (0.45 mA; 1 s), followed immediately by infusions of lidocaine hydrochloride or buffer (10 μg/0.25 μl). Retention was tested 2 days after training. Immediate posttraining infusions of lidocaine into the central nucleus did not affect retention performance; in contrast, immediate posttraining infusions of lidocaine into the basolateral complex significantly impaired retention performance. In addition, the effect of posttraining infusions of lidocaine into the basolateral complex was time-dependent: infusions administered 6 h after training also impaired memory, but infusions administered 24 h after training had no effect. Immediate posttraining infusions of lidocaine also impaired the retention performance of rats trained with a more intense footshock (0.75 mA). However, at the higher footshock intensity, administration of lidocaine 6 h after training had no effect on retention performance. The time- and footshock-dependent retrograde impairment of memory produced by posttraining reversible inactivation of the basolateral complex suggests that this region of the amygdala is involved in the consolidation of memory for inhibitory avoidance training.

γ- l-Glutamyl- l-aspartate induces specific deficits in long-term memory and inhibits [ 3H]glutamate binding on hippocampal membranes

γ- l-Glutamyl- l-aspartic acid (γ-LGLA) has been isolated from Datura stramonium; its structure has been determined and it was then synthesized. In male Swiss mice intraperitoneal administration of the natural peptide (125 nmol/kg) or of the synthetic peptide (25–2500 nmol/kg) 24 h after acquisition of a Y-maze avoidance task induced a dose-dependent deficit in retention performance 48 h later. γ-LGLA had no effect on locomotor activity or emotional reactivity at the doses used. Separate or simultaneous administration of aspartate or glutamate (each at 250 nmol/kg) had no effect on learning retention, indicating that deficit induced by γ-LGLA was specific to the peptide. γ-LGLA impaired learning acquisition in a time-dependent manner when administered juom 3 min to 24 h post-training, but had no effect when administered 3 days following acquisition. γ-LGLA administered just after the training session did not affect retention performance during the first 3 h, but suppressed the retention improvement observed in control animals from 6 to 24 h after acquisition; this deficit was still evident 7 days after the treatment. γ-LGLA partially inhibited l-[ 3H]glutamate binding on crude hippocampal or striatal membrane preparations; this inhibition was not observed on cerebellar membrane preparations. These results suggest a specific action of γ-LGLA on excitatory amino acid systems which may be responsible for its effects on learning retention.

Effect of novel experiences on retention of inhibitory avoidance behavior in mice: The influence of previous exposure to the same or another experience

Mice were trained and tested in a step-through inhibitory avoidance task with a 24-h interval between training and testing. At one of several intervals prior to the test session (9 h, 6 h, 3 h, or 6 min), they were given one of the following novel experiences: 4 min in a small Plexiglas box containing an empty water bottle, or 4 min hanging from the wire mesh ceiling of a large Plexiglas box. When given 3 h or 6 min before testing, both novel experiences enhanced retention test performance. The effect was antagonized by naltrexone and mimicked by an administration of beta-endorphin 6 min prior to testing. Thus, the findings are consistent with previous evidence suggesting that the effects of novel experiences on retention test performance are due to an activation of the brain beta-endorphin system. When one of the novel experiences given 3 h or 6 min prior to testing was preceded by the same experience given 6 h earlier retention test performance was not enhanced. Thus, the enhancing effect is obtained only if the experience is novel. Further, an experience given prior to retention testing did not affect performance if either the same or a different experience was given 3 h earlier. This finding is consistent with previous evidence indicating that following a novel experience, the brain beta-endorphin remains unresponsive for several hours. These results provide additional evidence that novel experiences prior to retention testing affect retention performance and provide additional support for the view that the effect may involve the release of beta-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)

Noradrenergic sympathetic blockade: Lack of effect on memory or retrograde amnesia

Previous results indicate that pretraining peripheral injections of any of several adrenergic receptor antagonists can attenuate retrograde amnesia. The present experiment was an attempt to determine if the attenuation of amnesia was due to a blocking of peripheral sympathetic norepinephrine release. This experiment examined the effects on cortical stimulation-induced amnesia of pretreatment with bretylium, a drug which blocks release of norepinephrine from sympathetic nerve endings. The findings indicate that bretylium does not itself affect retention performance, nor does bretylium attenuate the production of retrograde amnesia.

Enhancement and disruption of retention performance by ACTH in a choice task

One hundred twenty male rats escaped/avoided electric shock by moving into the lighted arm of a “Y” maze. Post-trial ACTH injections at one dose (1 IU/kg) enhanced retention (relative to saline controls), and at another dose (1000 IU/kg) disrupted retention; the overall dose-response function was an inverted “U” for the retention test conducted 24 hr after the original learning. Thus, ACTH was shown to affect retention performance of normal rats in a choice task. Delayed (4 hr) post-trial ACTH injections showed no enhanced or disrupted retention, from which it was concluded that ACTH acts upon some residual (memory?) from the learning experience.

Facilitation of retention performance in mice by posttraining diethyldithiocarbamate

These experiments examined the effects in mice of posttraining injections of diethyldithiocarbamate (DDC) upon retention (7 days after training) of active avoidance learning and upon whole brain catecholamine levels. When administered immediately following training, DDC enhanced retention performance. The degree of enhancement varied directly with the dose. DDC did not significantly affect retention performance if the injections were delayed 1 or 4 hours after training. Also, DDC administered 30 min prior to training did not affect retention performance. DDC (900 mg/kg) produced a large but transient increase in whole brain dopamine (DA) levels while norepinephrine (NE) levels were lowered.

Facilitation of time-dependent memory processes with posttrial epinephrine injections

This experiment examined the effect of posttraining epinephrine injections on memory-storage processes. Rats were trained with a weak footshock (0.7 mA, 0.35 sec) on a one-trial inhibitory avoidance task. The animals received epinephrine injections immediately, 10 min, 30 min, or 2 hr after training. On a retention test 24 hr after training, animals which received subcutaneous injections of epinephrine (0.01, 0.05, or 0.1 mg/kg) immediately after training had retention performance which was significantly better than that of saline control animals. A lower (0.001 mg/kg) or a higher (0.5 mg/kg) dose did not affect retention performance. Epinephrine injections (0.1 mg/kg) given 10 min after training also significantly facilitated retention, but injections given 30 min or 2 hr after training did not affect retention performance significantly. These findings suggest that the hormonal consequences of a training experience (e.g., epinephrine release) may normally modulate memory-storage processes in untreated animals.