Effect of ACTH,epinephrine, β-endorphin,naloxone, and of the combination of naloxone or β-endorphin with ACTH or epinephrine on memory consolidation

The effect on retention of the post-training intraperitoneal administration of ACTH_1–24 (0.2 or 2.0 μg/kg), epinephrine HC1 (5.0 or 50.0 μg/kg), human β-endorphin (0.1 or 1.0 μg/kg), naloxone (0.4 mg/kg), and of the combination of naloxine or β-endorphin with ACTH or epinephrine was studied in two different but closely related step-down inhibitory avoidance tasks in rats: task 1 (5 cm high 25 × 25 cm platform; 0.5 mA continuous footshock) and task 2 (7 × 25 cm platform, 0.3 mA discontinuous footshock). In task 1, saline control animals showed good retention in a test session carried out 24 hr later; β-endorphin, ACTH and epinephrine caused amnesia; β-endorphin potentiated the amnesic effect of ACTH and epinephrine; and naloxone caused memory facilitation and reversed the amnesic effect of ACTH and epinephrine. In task 2, control animals showed poor retention; β-endorphin caused amnesia at the dose of 0.1 but not 1.0 μg/kg; the other three drugs caused memory facilitation; naloxone potentiated the facilitatory effect of ACTH and epinephrine; and β-endorphin reversed it and transformed it into a deep amnesia.These findings suggest that an opioid-mediated amnesic mechanism modulates the effect of ACTH and epinephrine on memory consolidation, either by dampening that effect when training parameters tend to make it facilitatory, or by enhancing it when training conditions tend to make it amnesic. On the basis of these and previous data it seems likely that the amnesic effect of ACTH and epinephrine could be mediated by endogenous β-endorphin release.     

Influence on memory of posttraining or pre-test injections of ACTH, vasopressin, epinephrine, and beta-endorphin, and their interaction with naloxone

The intraperitoneal (i.p.) injection of ACTH 1-24 (0.2 microgram/kg), lysine--vasopressin (10.0 micrograms/kg) or epinephrine HCl (5.0 micrograms/kg) shortly after training or prior to testing caused memory facilitation of a step-down inhibitory avoidance task in rats, acquired with low intensity training footshocks (0.3 mA, 60 Hz). Naloxone HCl (0.4 mg/kg) potentiated their posttraining effect, but antagonized their pre-test effect. Naloxone on its own caused retrograde memory facilitation but had no effect on the test session. Posttraining human beta-endorphin (1.0 microgram/kg) was amnestic, and its pre-test administration enhanced retention. Both effects were naloxone-reversible. Neither the pre-test facilitation caused by beta-endorphin nor those caused by any of the other drugs (which are possible releasers of endogenous beta-endorphin) were observed in animals in which the influence of endogenous opioids was prevented at the posttraining period by the administration of naloxone. These results are compatible with, and considerably strengthen, the previously advanced hypothesis that learning of this task, and possibly others, depends on a state induced by beta-endorphin after training, and that it would normally be dissociated because this peptide is normally not released during test sessions. In addition, the posttraining facilitation caused by ACTH, vasopressin, and epinephrine stands out as an effect separate from, and in fact normally hindered by, posttraining beta-endorphin release.     

Naloxone attenuates amnesia caused by amygdaloid stimulation: The involvement of a central opioid system

This study investigated the effect of naloxone on amnesia produced by subseizure amygdaloid stimulation. Animals were trained in an inhibitory avoidance task, and given amygdaloid stimulation following training. Immediately after training, prior to stimulation, naloxone was injected either peripherally (i.p.) or into the bed nucleus of the stria terminalis (BNST) where the Met-enkephalin-containing fibers from the amygdala terminate. Amygdaloid stimulation caused retention deficits. The deficits were attenuated by 3.0 mg/kg naloxone given peripherally or by 1.0 microgram or 0.3 microgram naloxone injected bilaterally into the BNST. The attenuative effect was anatomically and receptor specific: 0.3 microgram of naloxone injected into the caudate nucleus was ineffective; the attenuative effect of naloxone was antagonized by simultaneous injection of 1.5 or 4.5 micrograms levorphanol into the BNST. These results suggest that endogenous opioids, possibly the enkephalins of the stria terminalis released into the BNST following amygdaloid stimulation, are at least partially involved in mediating the effect of amygdaloid stimulation on memory.     

Intense aversive training protects memory from the amnestic effects of hippocampal inactivation

There is extensive evidence that amnestic treatments are less effective, or ineffective when administered to subjects that have been overtrained or subjected to high foot‐shock intensities in aversively motivated learning. This protective effect has been found with a variety of learning tasks and with treatments that disrupt activity in several regions of the brain, including the hippocampus, amygdala, striatum, and substantia nigra. Such findings have been interpreted as suggesting that the brain regions disrupted are not critical sites for the memory processes induced by these types of training. In most experiments investigating this issue the amnestic treatments were administered after training. Thus, it might be less amnesia was induced because the training accelerated memory consolidation and, thus, the maximum effect of the amnestic treatment occurred after memory of the learning experience was consolidated. This study investigated this issue by inactivating the hippocampus of rats bilaterally with tetrodotoxin (TTX) (10 ng/side) 30 min before one‐trial inhibitory avoidance training using relatively low (1.0 mA), medium (2.0 mA), or high (3.0 mA) foot‐shock intensities. Retention of the task was measured 48 h after training. TTX produced a profound retention deficit, a mild deficit, and no deficit at all in the 1.0, 2.0, and 3.0 mA groups, respectively. These data confirm the protective effect of training with relatively high foot‐shock intensity against experimentally induced amnesia, and suggests that this protection is not due to accelerated consolidation. Rather, the findings suggest that strong training activates brain systems other than those typically involved in mediating memory consolidation. © 2013 Wiley Periodicals, Inc.     

Separable roles of hippocampal granule cells in forgetting and pyramidal cells in remembering spatial information

To investigate the roles individual hippocampal cell groups play in processing of spatial information for memory, we administered low-intensity electrical stimulation to the granule cells, CA3 and CA1 pyramidal cells of the dorsal hippocampus at selected times before and after acquisition of the solution to a radial maze win-stay task. Stimulation of any of the 3 cells populations yielded a variable duration anterograde disruption of memory performance, while stimulation of dentate gyrus granule cells alone produced a declarative memory-specific retrograde amnesia. The amnestic effect of granule cell stimulation was not associated with after discharges in the hippocampus and was prevented by systemic administration of the opiate antagonist naloxone. Our results support the view that this electrical stimulus does not disrupt, but rather, activates the normal function of the granule cell system, resulting in erasure of information held in declarative memory. In contrast, similar activation of the pyramidal cell system does not yield retrograde amnesia, suggesting a normal role for these cells in promoting memory for spatial information.     

Antagonism of endogenous opioids modulates memory processing

The studies reported here demonstrate that opioid antagonism enhances memory in two classes of animals viz. Aves and Mammalia. In mice, immediate posttraining administration of naloxone produces a time-dependent improvement in retention tested one week later. This effect is stereospecific. As naloxone was approximately 1000-fold more potent when administered intracerebroventricularly compared to subcutaneously, it appears that it produces its effect within the central nervous system. Pretest administration of naloxone, at a dose that failed to alter acquisition, also improved test performance, suggesting that naloxone also improved recall. Similar improvement in retention was demonstrated with the more potent opioid antagonist, nalmefene, at a 500-fold lower dose. The dose response to naloxone in both the mouse and the chick and to nalmefene in the mouse had the characteristics of an inverted U, with high doses either being ineffective or suppressing memory retention. In mice, naloxone demonstrated anti-amnestic properties against both anisomycin, a protein synthesis inhibitor, and scopolamine, an acetylcholine receptor blocker. Administration of beta-funaltrexamine (B-FNA) 72 h prior to training did not alter acquisition but did enhance retention. In studies where the mu-opioid receptor was blocked with B-FNA, naloxone was unable to enhance retention. B-FNA failed to impair the memory enhancing properties of arecoline, fluoxetine or clonidine. This demonstrates specificity of the B-FNA ability to prevent naloxone from enhancing memory and suggests that the opioid antagonist effects on memory are mediated by the mu-receptor.     

The effects of sulfated and nonsulfated cholecystokinin octapeptides on electroconvulsive shock-induced retrograde amnesia after intracerebroventricular administration in rats

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.     

Basolateral amygdala lesions block the memory-enhancing effect of 8-Br-cAMP infused into the entorhinal cortex of rats after training

There is extensive evidence suggesting that the basolateral nucleus of the amygdala plays a critical role in modulating memory consolidation processes in other brain regions. The present experiments examined interactions between the basolateral amygdala and the entorhinal cortex in modulating memory consolidation for inhibitory avoidance training. Several studies have reported that activation of the second messenger system adenosine 3',5'-cyclic monophosphate (cAMP) in several brain regions enhances memory and induces long-term plasticity. In the present experiments, a unilateral infusion of the cAMP analogue, 8-Br-cAMP (0.25 or 1.25 microg in 0.5 microL), administered into the entorhinal cortex of male Sprague-Dawley rats immediately after training, enhanced 48-h retention. An N-methyl-d-aspartate-induced lesion of the ipsilateral basolateral amygdala did not impair retention, but blocked the memory-enhancing effect of 8-Br-cAMP (infused into the entorhinal cortex) post-training. A lesion of the contralateral basolateral amygdala did not block the 8-Br-cAMP-induced retention enhancement. These findings indicate that an intact basolateral amygdala is essential for modulation of memory consolidation involving the entorhinal cortex, and are consistent with evidence that the basolateral amygdala regulates memory consolidation mediated by other brain regions.     

Peripheral epinephrine modulates the effects of post-training amygdala stimulation on memory

The present study investigated the role of adrenal epinephrine in the memory modulatory effects of post-training amygdala stimulation. Adrenal demedullated (ADMX) or sham demedullated (SHAM) rats received electrical stimulation of the amygdala immediately after training on inhibitory and active avoidance tasks. With both tasks, the stimulation impaired retention only in the rats with intact adrenal medullae: the retention performance of the ADMX in the rats with intact adrenal medullae: the retention performance of the ADMX rats given post-training stimulation was better than that of the unstimulated ADMX group with implanted electrodes. However, ADMX rats given post-training epinephrine (1.0 mg/kg, s.c.) immediately before the amygdala stimulation had retention deficits comparable to those of the SHAM group given amygdala stimulation. If epinephrine was administered a short time after rather than before the post-training amygdala stimulation, retention of the ADMX animals was not impaired. The findings are interpreted as indicating that circulating epinephrine present at the time of amygdala stimulation modulates the effects of amygdala stimulation on memory.     

Involvement of multiple opiate receptors in opioid kindling

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.     

Inhibition of long-term memory formation in the chicken by anti chick Thy-1 antibody

Anti-chick Thy-1 antibodies administered close to a single trial passive avoidance learning task in day-old chicks resulted in inhibition of long-term memory formation. The retention time course was comparable to that obtained with the protein synthesis inhibitor anisomycin. The amnestic effect of the anti-chick Thy-1 antibody appears to be mediated solely by immunoglobulin G, and is species specific since anti-rat Thy-1 antibodies did not produce amnesia. The results are consistent with a three stage model of memory formation, suggest a role for glycoproteins in long term memory formation, and emphasise the potential of neuroimmunological tools for investigating the neurological bases of memory formation.     

Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of amphetamine anorexia.

The brain mechanisms mediating amphetamine's suppressive effect on feeding behavior were analyzed in rats with chronically implanted brain cannulas. Experiments in which drugs were injected directly into the anterolateral hypothalamus, the region found to be most responsive to amphetamine's action, yielded the following results. (1) Over a dose range of 6.25 nmoles (0.8 mug) to 400 nmoles (51.4 mug), hypothalamically injected D-amphetamine produced a reliable suppression of food consumption (20 percent at 6.25 nmoles, increasing to 88 percent at 200 nmoles) and was found to be approximately 3 times as potent as L-amphetamine in yielding this effect. (2) The anorexic effect of hypothalamically injected D-amphetamine was totally abolished by local administration of alpha-methyltyrosine, an inhibitor of dopamine, norepinephrine, and perhaps epinephrine synthesis, or by local administration of Fla-63, an inhibitor of only norepinephrine, and perhaps epinephrine, synthesis. (3) This effect of hypothalamic D-amphetamine was also antagonized by locally administered dopaminergic or beta-adrenergic receptor blockers but was unaffected by alpha-adrenergic, serotonergic, and cholinergic blockers. (4) Lateral hypothalamic administration of dopaminergic or beta-adrenergic receptor blockers, at quite low doses, was also effective in antagonizing the anorexia induced by peripherally administered D-amphetamine. These results strongly suggest that amphetamine, in suppressing feeding behavior, acts through the lateral hypothalamus, perhaps the anterior region, causing a release of dopamine and norepinephrine (or perhaps epinephrine) from lateral hypothalamic nerve endings and a subsequent stimulation of dopaminergic and beta-adrenergic receptors located in that region.     

Involvement of amygdala pathways in the influence of post-training intra-amygdala norepinephrine and peripheral epinephrine on memory storage

These experiments examined the role of two major amygdala afferent-efferent pathways--the stria terminalis (ST) and the ventral amygdalofugal pathway (VAF)--in mediating the effects, on memory storage, of post-training intra-amygdala injections of norepinephrine (NE) and subcutaneous (s.c.) injections of epinephrine (E). Rats with either ST lesions or VAF transections and sham-operated rats were trained on a one-trial step-through inhibitory avoidance task and immediately after training received intra-amygdala injections of NE or a buffer solution. Other groups of VAF-transected animals received post-training s.c. injections of E or saline. ST lesions blocked the memory-enhancing effect of intra-amygdala injections of a low dose of NE (0.2 microgram) as well as the amnestic effect of a high dose of NE (5.0 microgram). In contrast, VAF transections did not block the memory-enhancing effect of NE (0.2 microgram). However, VAF transections attenuated the memory-enhancing effect of s.c. injections of E: the effective dose of E was shifted from 0.1 to 0.5 mg/kg. These findings, considered together with previous evidence that ST lesions block the memory-enhancing effect of peripheral E injections, suggest that the VAF is involved in mediating the central influence of peripheral E on amygdala functioning, while the ST is involved in mediating amygdala influences on memory storage elsewhere in the brain.     

Modulation of memory processing by neuropeptide Y varies with brain injection site

Neuropeptide Y (NPY) is a 36 amino acid peptide which was shown to enhance memory retention, recall and prevent amnesia induced by either scopolamine or anisomycin. In this study, we examined the effects of NPY administration into 6 areas of the mouse brain on memory retention for footshock avoidance training in a T-maze. NPY was injected into the rostral and caudal hippocampus, amygdala, caudate, septum and thalamus shortly after training. NPY improved retention when injected into the rostral portion of the hippocampus and septum, impaired retention in the caudal portion of the hippocampus and amygdala and had no effect in the thalamus and caudate. NPY was ineffective at either improving or impairing retention when injected 24 h after training, thus demonstrating that the effects of NPY on retention were time-dependent and not due to proactive effects on retention test performance per se. In addition, NPY had no effect on retention when injected into overlying cortical areas. NPY antibody impaired retention when administered into the rostral hippocampus and septum; it improved retention in the caudal hippocampus and amygdala. Thus NPY antibody had the opposite effect to that of NPY on memory retention suggesting that NPY has a physiological role as a modulator of memory processing within specific anatomical areas of the central nervous system.     

Basolateral Amygdala Lesions Block the Memory-enhancing Effect of Glucocorticoid Administration in the Dorsal Hippocampus of Rats

These experiments examined the effects of bilateral amygdala nuclei lesions on modulation of memory storage induced by bilateral intrahippocampal microinfusions of glucocorticoids in male Sprague-Dawley rats. Post-training infusions of the glucocorticoid receptor (type II) agonist RU 28362 (3.0 or 10.0 ng) enhanced inhibitory avoidance retention, and infusions of the glucocorticoid receptor antagonist RU 38486 (3.0 or 10.0 ng) administered shortly before training in a water maze spatial task did not affect acquisition, but impaired retention. In both tasks, neurochemically induced lesions of the basolateral but not of the central amygdala blocked the memory-modulatory effects of the intrahippocampal infusions of the drugs affecting glucocorticoid receptors. Lesions of the central amygdala alone impaired inhibitory avoidance retention, but basolateral amygdala lesions alone did not affect acquisition or retention in either task. These findings are consistent with previous evidence indicating that lesions of the basolateral amygdala block the memory-modulatory effects of systemically administered glucocorticoids, and provide further evidence that the basolateral amygdala is a critical area involved in regulating glucocorticoid effects in other brain regions involved in memory storage.     

Memory-enhancing effects of posttraining naloxone: involvement of beta-noradrenergic influences in the amygdaloid complex

Rats (220-250 g) were bilaterally implanted with cannulae in the amygdala, trained on an inhibitory avoidance response and two weeks later, on a Y-maze discrimination response. Immediately following the training on each task, they were injected intraperitoneally (i.p.) or intra-amygdally. Retention was tested one week after training for each task. Retention of the Y-maze task was assessed by discrimination reversal training. Naloxone administered i.p. (3.0 mg/kg) significantly facilitated retention of both tasks in unoperated control rats as well as in rats implanted bilaterally with amygdala cannulae. The memory-enhancing effect of naloxone i.p. was blocked by propranolol (0.3 or 1.0 microgram) injected in the amygdala, but not when this beta-noradrenergic antagonist was injected (0.3 micrograms) into either the caudate or the cortex dorsal to the amygdala. Further, intra-amygdala injections of the beta 1-adrenoceptor blocker atenolol (0.3 or 1.0 microgram) and the beta 2-adrenoceptor blocker zinterol (0.3 or 1.0 microgram), in doses which were ineffective when administered alone, blocked naloxone-induced (3.0 mg/kg, i.p.) memory facilitation. In contrast, posttraining intra-amygdala administration (1.0 micrograms) of the alpha-antagonists prazosin (alpha 1) or yohimbine (alpha 2) did not attenuate the memory-enhancing effects of systemically administered naloxone. These findings support the view that naloxone-induced enhancement of memory is mediated by the activation of beta- but not alpha-noradrenergic receptors located within the amygdaloid complex.     

Autonomic and endocrine participation in opioid peptide-induced hyperglycemia

Intracisternal administration of synthetic human beta-endorphin to conscious, ambulatory adult male rats caused dose-related increases in plasma glucose concentration. The largest dose of beta-endorphin examined, 7.25 nmol, increased plasma glucose concentration within 7 min and this effect lasted 2.5 h. On the other hand, only 58 pmol was required to induce transient hyperglycemia, when compared to the response observed in saline-injected control rats. This hyperglycemic effect of beta-endorphin was prevented by prior systemic administration of naloxone, thus supporting the hypothesis that this beta-endorphin-induced effect is mediated at opioid receptors. beta-Endorphin also markedly increased plasma concentrations of epinephrine, norepinephrine and, to a lesser extent, dopamine. A significant positive correlation was demonstrated between plasma glucose and plasma epinephrine responses to increasing doses of intracisternally administered beta-endorphin. In addition, intracisternal beta-endorphin also increased plasma glucagon concentration without significantly increasing plasma insulin concentration. Thus, it is probable that epinephrine and glucagon are the major factors mediating this hyperglycemic effect. beta-Endorphin-induced hyperglycemia was prevented by ganglionic blockade with chlorisondamine. This further supports the thesis that intracerebral beta-endorphin increases plasma glucose concentration by activation of the central autonomic outflow. In addition to these effects on short-term regulators of glycemia, intracisternal beta-endorphin increased plasma concentrations of corticosterone and growth hormone. Both of these glucose counterregulatory hormones may play minor roles in modulating beta-endorphin-induced hyperglycemia.     

Mu receptors at discrete hypothalamic and brainstem sites mediate opioid peptide-induced increases in central sympathetic outflow

Synthetic human beta-endorphin, 7.25 nmol intracisternally, in conscious, freely moving, cannulated adult male rats increased plasma concentrations of the 3 catecholamines, epinephrine, norepinephrine and dopamine. Similarly administered equimolar morphine increased only plasma epinephrine concentration significantly. A 10-fold greater intracisternal dose of morphine significantly increased plasma concentrations of all 3 catecholamines. This effect was inhibited by prior intra-arterial naloxone administration. Intracisternal administration of the selective mu receptor agonist [D-Ala2,NMe-Phe4,Gly-ol5]enkephalin (DAGO), 2.9 nmol, also increased plasma concentrations of the 3 catecholamines and, furthermore, these effects were significantly greater than those noted in response to equimolar beta-endorphin. The greater potency of DAGO than beta-endorphin to increase catecholamine secretion suggests that this opioid peptide-induced effect is mediated at mu receptors. Administration of DAGO, 0.1 nmol, directly into either the hypothalamic paraventricular nucleus (PVN) or brainstem nucleus of the solitary tract (NTS) significantly increased plasma concentrations of all 3 catecholamines when compared with either saline-infused controls or animals administered DAGO into other brain areas. These catecholamine-stimulating effects of DAGO administered into either PVN or NTS were prevented by prior intra-arterial naloxone administration. Heart rate, but not mean arterial blood pressure, increased in response to DAGO administration into the NTS while no significant cardiovascular changes were noted among the experimental groups in response to DAGO administered into the PVN. These data support a hypothesis that mu receptors at discrete and anatomically distant brain sites mediate opioid peptide-induced catecholamine secretion through activation of the central sympathetic outflow to the adrenal medulla and sympathetic nerve terminals.     

Peripheral steroid sulfatase inhibition potentiates improvement of memory retention for hippocampally administered dehydroepiandrosterone sulfate but not pregnenolone sulfate

Dehydroepiandrosterone sulfate (DHEAS) improves memory retention when administered peripherally. Estrone-3-O-sulfamate (EMATE), a steroid sulfatase inhibitor, potentiates the effect of DHEAS on memory retention such that lower doses of DHEAS improve memory retention. It is not clear if this effect is mediated by both compounds entering the central nervous system. In the current studies, mice were trained to avoid footshock in a T-maze and memory retention was tested 1 week later. DHEAS, injected into the hippocampus after training, improved memory retention in a dose-dependent manner. In previous studies, pregnenolone sulfate (PREGS) improved memory retention when injected into the hippocampus. EMATE, administered peripherally, potentiated the effect of centrally administered DHEAS on memory retention. However, EMATE did not potentiate the effect of centrally administered PREGS. It was concluded that EMATE, acting peripherally, increased plasma levels of DHEAS which entered the brain and added to the effect of centrally administered DHEAS. The failure of EMATE to potentiate PREGS is discussed.     

Intracerebroventricular administration of nanogram amounts of beta-endorphin and Met-enkephalin causes retrograde amnesia in rats

The intracerebroventricular (icv) administration of 5.0 or 25.0 ng of beta-endorphin or Met-enkephalin causes retrograde amnesia for a shuttle avoidance task ion rats. In both cases, the higher dose was more effective than the lower one. The present results confirm previous similar findings obtained using systemic administrations of these compounds, and suggest that the amnestic effect of beta-endorphin and Met-enkephalin is mediated centrally.