Drug-induced Amnesia Research Articles

What is it like to be unitarily reversed?

There has been in recent years a huge surge of interest in the so-called extended Wigner’s friend scenario (EWFS). In short, a series of theorems (with some variation in detail) puts pressure on the ability of different agents in the scenario to account for each of the others’ measured outcomes: the outcomes cannot be assigned single well-defined values while also satisfying other reasonable physical assumptions. These theorems have been interpreted as showing that there can be no absolute, third-person, ‘God’s eye’ description of our reality. The focus of this paper is the strongest of these no-go theorems, the ‘local friendliness’ theorem of Bong et al. (2020, Nature Physics, 16, 1199–1205), which gives earnest consideration to the possibility of a measurement that unitarily reverses an entire lab system, including a conscious agent, thereby erasing the agent’s memory. The purpose of this paper is to begin the philosophical conversation regarding key questions concerning this process: Are the events in the lab merely ‘erased’, or do they in some sense not exist at all? What would it be like to be unitarily reversed? Should an agent care about any experiences they have inside the lab before they are reversed? This analysis employs a parallel case of memory erasure, to which this case can be contrasted, arising in the context of drug-induced amnesia as a result of administering anaesthesia during medical procedures (Carbonell, 2014, Bioethics, 28(5), 245–254). I argue that the consequences of unitarily reversing an agent are much more dramatic than simply memory erasure—the set of events themselves, and the personal timeline of the agent, leave no record at all inside or outside the lab. I consider the ramifications of this for the picture of reality that arises from the EWFS.

Apparent reconsolidation interference without generalized amnesia

Memories remain dynamic after consolidation, and when reactivated, they can be rendered vulnerable to various pharmacological agents that disrupt the later expression of memory (i.e., amnesia). Such drug-induced post-reactivation amnesia has traditionally been studied in AAA experimental designs, where a memory is initially created for a stimulus A (be it a singular cue or a context) and later reactivated and tested through exposure to the exact same stimulus. Using a contextual fear conditioning procedure in rats and midazolam as amnestic agent, we recently demonstrated that drug-induced amnesia can also be obtained when memories are reactivated through exposure to a generalization stimulus (GS, context B) and later tested for that same generalization stimulus (ABB design). However, this amnestic intervention leaves fear expression intact when at test animals are instead presented with the original training stimulus (ABA design) or a novel generalization stimulus (ABC design). The underlying mechanisms of post-reactivation memory malleability and of MDZ-induced amnesia for a generalization context remain largely unknown. Here, we evaluated whether, like typical CS-mediated (or AAA) post-reactivation amnesia, GS-mediated (ABB) post-reactivation amnesia displays key features of a destabilization-based phenomenon. We first show that ABB post-reactivation amnesia is critically dependent on prediction error at the time of memory reactivation and provide evidence for its temporally graded nature. In line with the known role of GluN2B-NMDA receptor activation in memory destabilization, we further demonstrate that pre-reactivation administration of ifenprodil, a selective antagonist of GluN2B-NMDA receptors, prevents MDZ-induced ABB amnesia. In sum, our data reveal that ABB MDZ-induced post-reactivation amnesia exhibits the hallmark features of a destabilization-dependent phenomenon. Implication of our findings for a reconsolidation-based account of post-reactivation amnesia are discussed.

Limited replicability of drug-induced amnesia after contextual fear memory retrieval in rats.

With the ultimate goal of investigating boundary conditions for post-reactivation amnesia, we set out to replicate studies in which systemic, post-reactivation administration of midazolam, propranolol, or cycloheximide resulted in amnesia for contextual fear memories. Our experiments involved conceptual as well as exact replications of previously published studies. In most of our experiments, we adopted a procedure that conformed to the standard 3-day protocol typically used in the literature, with contextual fear conditioning on day 1, unreinforced re-exposure to the conditioning context followed by systemic injection of the amnestic drug on day 2, and a memory retention test on day 3. Given the plethora of successful studies with large effects sizes and the absence of any failed replications in the literature, we were surprised to find that we were generally unable to replicate those findings. Our results suggest that post-reactivation amnesia by systemic drug administration in rats is more difficult to obtain than what would be expected based on published empirical reports. At present, it remains unclear which conditions determine the success of this procedure.

마우스에서 국내 육성 신품종 ‘신예감’ 추출물의 기억력 증진 효과

A new mandarin hybrid cultivar called ‘Shinyegam’ was developed from a cross between ‘Kiyomi’ (Citrus unshiu × C. sinensis) and ‘Wilking’ (Citrus reticulata) at the Citrus Research Institute of the National Institute of Horticultural and Herbal Science in 2012. The ‘Shinyegam’ was extracted with 70% ethanol (SYGE), and polyphenol content was measured to assess total antioxidant activity of flavonoids. Radical scavenging activities of the extracts were examined using a-a-diphenyl-β-picrylhydrazyl (DPPH), 2,2-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays. SYGE showed high polyphenol and flavonoid content as well as strong DPPH, ABTS, and FRAP radical scavenging activity. We used a mouse model to assess the memory enhancing properties of SYGE and its ameliorating activities on learning and memory impairments. Drug-induced amnesia was initiated by scopolamine treatment (2 mg/kg, interperitoneal). SYGE administration (25 mg/kg, oral) significantly enhanced cognitive function and attenuated scopolamine-induced cognitive impairments as determined by novel object recognition, passive avoidance and Y-maze tasks. In addition, SYGE increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These results suggest that SYGE enhances learning and memory in normal states and attenuates memory loss caused by cholinergic dysfunction.

EFFECT OF METFORMIN AND SIMVASTATIN IN DIAZEPAM-AND SODIUM NITRITE-INDUCED ANTEROGRADE AMNESIA IN MALE SWISS ALBINO MICE

Objective: To study the effect of metformin and simvastatin on diazepam-and sodium nitrite-induced anterograde amnesia in male Swiss albino mice.Methods: A total of 56 healthy male Swiss albino mice weighing 20–30 g were included in the study Mice were divided into seven groups (n=8) and received a specific dosage of drugs including metformin and simvastatin. Anterograde amnesia was induced by diazepam and sodium nitrite. Morris water maze paradigm was used to study amnesia in which the mice were trained to locate a hidden platform by releasing them into the opaque water for four times a day for four consecutive days. The acquisition of this task was evaluated by measuring escape latency time on all the days of study and by measuring the index of retrieval on day 5 of the study. These observations were compared among the test groups and drug-induced amnesia groups. The time was expressed as mean±standard error of the mean.Results: Significant reduction in the mean escape latency time (25.25 ± 5.09 s) and index of retrieval (52.38 ± 3.55 s) was observed in groups administered with sodium nitrite and metformin (p<0.001). In groups administered with sodium nitrite and simvastatin, the mean escape latency time and index of retrieval were 47.66 ± 7.69 s and 40.75 ± 4.13 s, respectively (p<0.05)). In addition, metformin completely ameliorated sodium nitrite-induced anterograde amnesia.Conclusion: Metformin and simvastatin ameliorated sodium nitrite-induced anterograde amnesia pointing toward a possible antioxidant role and can, therefore, be used to potentially inhibit oxidative stress-induced neurodegeneration. However, the pleiotropic roles of metformin and simvastatin are the areas that warrant further investigation before their clinical use.

Effect of nucleus accumbens shell 5-HT4 receptors on the impairment of ACPA-induced emotional memory consolidation in male Wistar rats.

The present study investigates the effects of 5-HT4 receptors of the nucleus accumbens (NAc) shell on the impairment of emotional memory consolidation induced by cannabinoid CB1 receptor stimulation. The elevated plus maze test-retest paradigm was used to assess memory in adult male Wistar rats. Intra-NAc shell administration of ACPA (selective cannabinoid CB1 receptor agonist 0.006 µg/rat) and RS23597 (5-HT4 receptor antagonist 0.01 µg/rat), immediately after training, decreased emotional memory consolidation, suggesting a drug-induced amnesia, whereas post-training intra-NAc shell microinjections of RS67333 (5-HT4 receptor agonist 0.016 µg/rat) increased emotional memory consolidation. Interestingly, RS67333 exerted a dual effect on ACPA-induced behaviors, potentiating and restoring amnesia caused by the subthreshold and effective doses of ACPA, respectively. However, neither RS23597 nor AM251 (CB1 receptor antagonist 30, 60 and 120 ng/rat) affected emotional memory consolidation. Nonetheless, a subthreshold dose of AM251 (120 ng/rat) reversed the amnesia induced by ACPA (0.006 µg/rat) and RS23597 (0.01 µg/rat). None of the above doses altered the locomotor activity. In conclusion, our results suggest that the NAc-shell 5-HT4 receptors are involved in the modulation of ACPA-induced amnesia.

Antiamnesic Effect of Actinidia arguta Extract Intake in a Mouse Model of TMT-Induced Learning and Memory Dysfunction.

The antiamnesic effects of ethyl acetate fraction from Actinidia arguta (EFAA) on trimethyltin- (TMT-) induced memory impairment were investigated to find the possibility of functional food substances. EFAA showed a potent AChE inhibitory effect (IC50 = 53 μg/mL) and efficient neuroprotection against H2O2-induced oxidative stress. The administration of EFAA significantly decreased TMT-induced cognitive deficit in Y-maze, passive avoidance, and Morris water maze (MWM) tests. After the behavioral tests, the antioxidant activities were confirmed using mice brain tissues. EFAA not only showed the inhibition of AChE activity and the decline of malondialdehyde (MDA) level as a sign of lipid peroxidation but also presented the increase of the superoxide dismutase (SOD) level and the decrease of the oxidized glutathione (GSSG)/total glutathione (GSH + GSSG) ratio. Finally, the phenolics in EFAA were identified using liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, and four main phenolics, such as quinic acid, chlorogenic acid, caffeoyl hexose, and quercetin-3-glucoside, were identified. These results suggest that EFAA containing physiological phenolics might enhance drug-induced amnesia through AChE inhibition and neuroprotection.

Scientific Evidence for Korean Medicine and Its Integrative Medical Research

Scientific Evidence for Korean Medicine and Its Integrative Medical Research

Midazolam and atropine alter theta oscillations in the hippocampal CA1 region by modulating both the somatic and distal dendritic dipoles.

Theta (4-12 Hz) oscillations in the hippocampus play an important role in learning and memory. They are altered by a wide variety of drugs that impair memory, and these effects may underlie or contribute to drug-induced amnesia. However, the network mechanisms linking drug actions with changes in memory formation remain poorly defined. Here, we used a multisite linear electrode array to measure local field potentials simultaneously across the CA1 layers of the hippocampus during active exploration, and employed current source density analysis and computational modeling to investigate how midazolam and atropine-two amnestic drugs that are used clinically and experimentally-change the relative timing and strength of the drivers of θ-oscillations. We found that two dipoles are present, with active inputs that are centered at the soma and the distal apical dendrite and passive return pathways that overlap in the mid-apical dendrite. Both drugs shifted the position of the phase reversal in the local field potential that occurred in the mid-apical dendritic region, but in opposite directions, by changing the strength of the dendritic pole, without altering the somatic pole or relative timing. Computational modeling showed that this constellation of changes, as well as an additional effect on a variably present mid-apical pole, could be produced by simultaneous changes in the active somatic and distal dendritic inputs. These network-level changes, produced by two amnestic drugs that target different types of receptors, may thus serve as a common basis for impaired memory encoding.

시판 초석잠 기원식물의 기억력개선효과 비교연구

Objectives : The purpose of this study was to characterize the effect of the Ethanolic extract of Stachys sieboldii and Lycopus lucidus on the learning and memory impairments induced by scopolamine. Methods : The genetic difference of Stachys sieboldii and Lycopus lucidus were observed with RAPD analysis. The cognition-enhancing effect of Stachys sieboldii and Lycopus lucidus was investigated using a passive avoidance test, Y-maze test and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Results : As a result of RAPD analysis, Stachys sieboldii and Lycopus lucidus Radix was found to be genetically different and The results of learning memory analysis showed that Stachys sieboldii extract-treated group (500 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Passive avoidance Y-maze test and Water maze test. And these results are same manner in DPPH radical scavenger effect and Acetylcholineseterase inhibition effect. These results suggest that Stachys sieboldii extract maybe a useful cognitive impairment treatment, and its beneficial effects are depending on the origin plants. Conclusions : Commercially available Stachys sieboldii Radix consists of two original plant, one of them people misuse. To clarify the origin of the plant Memory tests were performed. These results suggest that 80% Ethanol extract of Stachys sieboldii showed significant anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent of the learning models.

발효에 의한 길경추출물의 인지기능 개선 효능

Objectives : The purpose of this study was to characterize the effect of the Ethanolic extracts of Platycodon grandiflorum and its permented production the learning and memory impairments induced by scopolamine. Methods : The cognition-enhancing effect of Platycodon grandiflorum and its permented production were investigated using a passive avoidance test, the Morris water maze test and Y-maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Results : The results showed that the Permented Platycodon grandiflorum extract-treated group (100 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Passive avoidance Y-maze test and Water maze test. And these results are same manner in DPPH radical scavenger effect and Acetylcholineseterase inhibition effect. Conclusions : These results suggest that 80% Ethanol extract of fermented P.grandiflorum showed significant anti-amnestic and cognitive-enhancing activities related to the memory processes, and these activities were parallel to treatment duration and dependent of the learning models.

포공영 기원식물의 mouse 기억력 개선효과 비교

ABSTRACT Objectives : The purpose of this study was to characterize the effect of the fraction of Taraxacum officinale and T.coreanum on the learning and memory impairments induced by scopolamine.Methods : The cognition-enhancing effect of Taraxacum officinale and T.coreanum was investigated using a passive avoidance test, the Morris water maze test and Y-maze t est in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.).Results : The results showed that the Aug harvested T.offiicinale extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly amelio rated scopolamine-induced amnesia based on the Passive avoidance Y-maze test and Watermaze test. And these res ults are same manner in DPPH radical scavenger effect and Acetylcholineseterase inhibition effect. Conclusions : These results suggest that Taraxacum officinale extract maybe a useful cognitive impairment treatment, and its beneficial effects are depending on the coll ecting time and origin plants. As a result, Taraxacum officinale harvested in August improve memory most. Key words : Taraxacum officinale, Collecting time, Memory enhancing, scopolamine

Amnesia, Anesthesia, and Warranted Fear

Is a painful experience less bad for you if you will not remember it? Do you have less reason to fear it? These questions bear on how we think about medical procedures and surgeries that use an anesthesia regimen that leaves patients conscious - and potentially in pain - but results in complete 'drug-induced amnesia' after the fact. I argue that drug-induced amnesia does not render a painful medical procedure a less fitting object of fear, and thus the prospect of amnesia does not give patients a reason not to fear it. I expose three mistakes in reasoning that might explain our tendency to view pain or discomfort as less fearful in virtue of expected amnesia: a mistaken view of personal identity; a mistaken view of the target of anticipation; and a mistaken method of incorporating past evidence into calculations about future experiences. Ultimately my argument has implications for whether particular procedures are justified and how medical professionals should speak with anxious patients about the prospect of drug-induced amnesia.

Activation of dopamine D1 receptors in the medial septum improves scopolamine-induced amnesia in the dorsal hippocampus

In the present study, we investigated the influence of intra-medial septum (intra-MS) injections of dopamine D1 receptor agents on amnesia induced by intra-CA1 injections of a muscarinic acetylcholine receptor antagonist, scopolamine. This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that in the animals that received post-training intra-MS injections of saline, intra-CA1 administrations of scopolamine (0.75, 1, and 2μg/rat) decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-MS injections of a dopamine D1 receptor agonist, SKF38393 at doses of 0.1, 0.15, and 0.3μg/rat had no effect, but at dose of 0.5μg/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5μg/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1μg/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75μg/rat) by itself impaired IA memory consolidation, and also at dose of 0.75μg/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5μg/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5μg/rat) prevented an effective dose of SKF38393 response to the impaired effect of scopolamine. These results suggest that dopamine D1 receptors in the MS via projection neurons to the hippocampus affect impairment of memory consolidation induced by intra-CA injections of scopolamine.

기억력 감퇴 모델에서 영신초(靈神草), 원지(遠志), 석창포(石菖蒲) 혼합제제의 기억력 및 인지 기능 개선에 관한 연구

In the present study, we assessed the effect of the PPA (Polygala japonica Houtt., Polygala tenuifolia WILLD. and Acorus gramineus SOLAND. mixed preparation), a traditional herbal prescription, on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of PPA was investigated using a passive avoidance test, Y-maze test and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). A single PPA (400 and 800 (mg/kg)) administration significantly reversed the scopolamine-induced cognitive impairments in the passive avoidance test (P

Cognitive dysfunctions induced by a cholinergic blockade and Aβ25–35 peptide are attenuated by salvianolic acid B

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-β (Aβ)25–35 peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Aβ25–35 (10 nmol/5 μl, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABAA receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 μM) was found to inhibit GABA-induced outward Cl− currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Aβ25–35-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.

Oxycodone dose-dependently imparts conditioned reinforcing properties to discrete sensory stimuli in rats

The aim of this study was to explore the psychopharmacological characteristics of opioid-induced conditioned reinforcement using oxycodone, a potent mu-opioid receptor agonist with known abuse potential. In differed groups of rats, passive intravenous infusions of oxycodone (100 infusions/3 h × 6 sessions in total; 0, 0.01, 0.05 and 0.1 mg/kg/inf) were paired with an audio–visual stimulus and, subsequently, operant responding maintained by this conditioned stimulus was tested in extinction conditions. It was found that the oxycodone-paired stimulus maintained operant responding and that this effect was dependent on the number of conditioning sessions and on the conditioning dose. Responding maintained the oxycodone-paired stimulus could also be reinstated by both foot-shock stress and by oxycodone priming (0.25 mg/kg, SC). A conditioned place preference experiment (3 drug and 3 vehicle injections over 6 days; oxycodone: 0, 0.25, 2 and 5 mg/kg, SC) confirmed that stimuli associated with lower doses of oxycodone induce conditioned approach. Finally, two control experiments performed with chlordiazepoxide ruled out an interpretation of the oxycodone data based on drug-induced amnesia, and confirmed that operant responding for a drug-conditioned stimulus is observed only when the drug possesses unconditioned reinforcing properties. Therefore, the intravenous conditioned reinforcement procedure appears a useful method to study how opioid drugs impart reinforcing value to discrete environmental stimuli.

공진단(拱辰丹)과 영신초(靈神草), 원지(遠志), 석창포(石菖蒲) 혼합제제의 기억력과 인지기능 개선 및 항불안에 관한 연구

Objectives : The purpose of this study was to characterize the neuroprotective effects and anxiolytic-like effects of Gongjin-dan and Polygala japonica, Polygala tenuifolia, Acorus gramineus mixed pills(G.J.D-P.P.A.). Methods : The neuroprotective effects of G.J.D-P.P.A. determined by the passive avoidance and Y-maze tasks and Morris water maze task, and the anxiolytic-like effects of the G.J.D-P.P.A. using an elevated plus-maze(EPM) in mice. Results : Drug-induced amnesia was induced by treating animals with scopolamine(1 mg/kg, i.p.). A single G.J.D-P.P.A.(400 and 800 mg/kg) administration significantly enhanced cognitive function and attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks(P

Activation of cannabinoid CB1 receptors in the central amygdala impairs inhibitory avoidance memory consolidation via NMDA receptors

In the present study, we investigated the influence of bilateral intra-central amygdala (intra-CeA) microinjections of N-methyl-d-aspartate (NMDA) receptor agents on amnesia induced by a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA). This study used a step-through inhibitory (passive) avoidance task to assess memory in adult male Wistar rats. The results showed that intra-CeA administration of ACPA (2ng/rat) immediately after training decreased inhibitory avoidance (IA) memory consolidation as evidenced by a decrease in step-through latency on the test day, which was suggestive of drug-induced amnesia. Post-training intra-CeA microinjections of NMDA (0.0001, 0.001 and 0.01μg/rat) did not affect IA memory consolidation. However co-administration of NMDA with ACPA (2ng/rat) prevented the impairment of IA memory consolidation that was induced by ACPA. Although post-training intra-CeA administration of the NMDA receptor antagonist, d-(−)-2-amino-5-phosphonopentanoic acid (d-AP5; 0.01, 0.05 and 0.1μg/rat) alone had no effect, its co-administration with an ineffective dose of ACPA (1ng/rat) impaired IA memory consolidation. Post-training intra-CeA microinjection of an ineffective dose of d-AP5 (0.01μg/rat) prevented an NMDA response to the impaired effect of ACPA. These results suggest that amnesia induced by intra-CeA administration of ACPA is at least partly mediated through an NMDA receptor mechanism in the Ce-A.

Dose effects of triazolam and scopolamine on metamemory.

The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one's own memory) in a two-phase paradigm designed to assess effects on both monitoring and control components of metamemory in both semantic (general knowledge) and episodic memory (cued-recall) tasks. Placebo and 2 doses each of triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg, subcutaneous) were administered to 80 healthy volunteers (16 per group) in a double-blind, double-dummy, independent groups design. Both triazolam and scopolamine impaired episodic memory (quantity and accuracy) but not semantic memory. Results suggested that both drugs impaired monitoring as reflected in absolute accuracy measures (impaired calibration in the direction of overconfidence) and control sensitivity (the relationship between confidence and behavior). Overall, the results did not provide evidence for differences between triazolam and scopolamine in memory or metamemory. In addition to the clinical relevance of the observed effects, this study adds to the accumulating body of cognitive psychopharmacological research illustrating the usefulness of drug-induced amnesia as a vehicle to explore memory and metamemory.