Pyroglutamic acid improves learning and memory capacities in old rats

The effects of the arginine salt of pyroglutamic acid (2-oxo-pyrrolidone carboxylic acid, PCA) on learning and memory capacities of old rats were studied in a subchronic treatment schedule (i.p. injection of 0.1 and 1 g/kg/day for 15 days). The acquisition and extinction of active avoidance behaviour were studied in a pole-jumping test situation. The retention of passive avoidance response was examined in a step-through passive avoidance task. PCA facilitated the rate of acquisition of pole-jumping response, and inhibited the extinction of the response. The dose of 1 g/kg was more potent than 0.1 g/kg in this respect. Also in the passive avoidance task, the treatment with PCA was followed by an improvement of avoidance retention. These results indicate that PCA is a behaviourally active compound in that it improves learning and memory capacities in old rat.     

Synergistic improvement effect of nicotine-ghrelin co-injection into the anterior ventral tegmental area on morphine-induced amnesia

In the present study the effect of ghrelin or ghrelin/nicotine injection into the anterior ventral tegmental area (aVTA) on morphine-induced amnesia in passive avoidance learning have been evaluated. Also, the role of the aVTA nicotinic receptors in possible ghrelin-induced effects has been investigated. All animals were bilaterally implanted with chronic cannulas in the aVTA. A step-through type passive avoidance task was used for measurement of memory. We found that post-training subcutaneous (s.c.) injection of morphine (0.5–7.5 mg/kg) dose-dependently reduced the step-through latency, indicating morphine-induced amnesia. Post-training bilateral infusion of ghrelin (0.3, 1.5 and 3 nmol/μl) in a dose-dependent manner reversed amnesia induced by morphine (7.5 mg/kg, s.c.). Furthermore, reversal effect of ghrelin (3 nmol/μl) was blocked by pre-treatment of intra-aVTA administration of mecamylamine (1–3 μg/rat), a nicotinic acetylcholine receptor antagonist. Intra-aVTA administration of the higher dose of mecamylamine (3 μg/rat) into the aVTA by itself decreased the step-through latency and induced amnesia. In addition, post-training intra-aVTA administration of nicotine (0.25, 0.5, 1 μg/rat) which alone cannot affect memory consolidation, decreased significantly the amnesia induced by morphine (7.5 mg/kg, s.c.). Co-treatment of an ineffective dose of ghrelin (0.3 nmol/μl) with an ineffective dose of nicotine (0.25 μg/rat) significantly increased step-through latency of morphine (7.5 mg/kg, s.c.) treated animals, indicating the synergistic effect of the drugs. Taken together, our results suggest that intra-aVTA administration of ghrelin reversed morphine-induced amnesia and that ghrelin interacts synergistically with nicotine to mitigate morphine-induced amnesia.     

The effects of rutin on a passive avoidance test in rats

Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The aim of the present study was to investigate the effects of rutin (3, 3′, 4′, 5, 7-pentahydroxyflavone-3-rhamnoglucoside), a flavonoid that is an important dietary constituent of foods and plant-based beverages, on memory retrieval in rats. To this end, we assessed the effect of rutin on memory retrieval using a step-through passive avoidance task. Rutin (5, 10, and 100 mg/kg) was administered intraperitoneally (i.p.) one week before the start of training. Three retention tests were performed to assess memory in rats. Rutin (10 mg/kg) significantly increased the step-through latency of the passive avoidance response compared to the control in the three retention tests of the passive avoidance paradigm. These results indicate that rutin has a potential role in enhancing memory retrieval. Several mechanisms may contribute to the potential role of rutin in memory enhancement. This result supports the potential beneficial effects of rutin as a dietary supplement on memory retrieval in a passive avoidance task.     

Enhancing effects of chronic lithium on memory in the rat

BACKGROUND: In spite of recent enrichment of neurochemical and behavioural data establishing a neuroprotective role for lithium, its primary effects on cognitive functioning remain ambiguous. This study examines chronic lithium effects on spatial working memory and long-term retention. METHODS: In three discrete experiments, rats subjected to 30 daily intraperitoneal injections (2mmol/kg) of lithium (lithium groups: serum lithium=0.5+/-0.4mEq/l, 12h post-injection) or saline (controls) were trained in 0-s delay T-maze alternation and then tested in 30-, 45- and 60-s delay alternation (Experiments 1, 2, 3, respectively). Animals from Experiment 1 were further tested in one-trial step-through passive avoidance under mild shock parameters (0.5mA, 1s). Retention was assessed 6h later. Daily lithium or saline injections continued throughout behavioural testing. RESULTS: Lithium animals were indistinguishable from controls during 0-delay alternation baseline (Experiments 1-3, accuracy>88%) but showed significantly higher accuracy than controls at 30- and 45-s delays (93% versus 85% and 92% versus 82%, Experiments 1 and 2, respectively). At 60-s delay (Experiment 3) this beneficial effect of lithium was no longer apparent (lithium and control accuracy=78%). In Experiment 4, the shock used did not support 6-h passive avoidance retention in controls, whereas lithium animals showed significant step-through latency increases. CONCLUSIONS: Chronic lithium enhanced spatial working memory and promoted long-term retention of a weak aversive contingency. The results suggest that lithium may have potential as a cognitive enhancer.     

Nociceptin system plays a role in the memory retention: involvement of naloxone benzoylhydrazone binding sites.

We investigated the role of nociceptin system in learning and memory in mice. The deficiency of nociceptin receptors and nociceptin itself did not affect the alternation behavior in the Y-maze test. In the passive avoidance test, the step-through latencies of nociceptin receptor knockout mice were longer than those of wild-type mice. Nociceptin shortened the step-through latency in wild-type mice. This impairment on passive avoidance task was reversed by naloxone benzoylhydrazone (NalBzoH), indicating that the amnesic effects of nociceptin may be mediated through the NalBzoH recognition sites. These suggest that nociceptin system plays an important role in the memory retention of passive avoidance task, and NalBzoH-recognized sites are involved in nociceptin-induced impairment of the memory retention.     

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 2 μg/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 0.3 μg/rat had no effect, but at dose of 0.5 μg/rat impaired IA memory consolidation. Interestingly, intra-MS injections of SKF38393 (0.15, 0.3 and 0.5 μg/rat) significantly prevented amnesia induced by intra-CA1 injections of scopolamine (1 μg/rat). Intra-MS injections of a dopamine D1 receptor antagonist, SCH23390 (0.5 and 0.75 μg/rat) by itself impaired IA memory consolidation, and also at dose of 0.75 μg/rat increased amnesia induced by intra-CA1 administrations of an ineffective dose of scopolamine (0.5 μg/rat). Post-training intra-MS injections of ineffective doses of SCH23390 (0.1, 0.3 and 0.5 μg/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.     

GSK3抑制剂氯化锂对脆性X综合征模型小鼠避暗行为的干预作用

目的探讨糖原合成酶激酶3(glycogen synthase kinase3,GSK3)抑制剂氯化锂对脆性X综合症小鼠模型的避暗行为的干预作用及机制。方法通过对30日龄脆性X综合症小鼠连续腹腔注射不同剂量氯化锂5 d,用药第4天和第5天进行避暗实验;同时用免疫印迹技术检测Fmr1 knockout(KO)及wild type(WT)小鼠的海马和皮层总GSK 3β和磷酸化GSK 3β(P-GSK3β)的变化。结果在避暗实验中,KO鼠与WT鼠,两者潜伏期及错误次数分别为(56±32)s,(83±24)s;(7±3)次,(3±2)次;免疫印迹实验结果:KO鼠皮层及海马P-GSK3β表达平均灰度值分别为69,63;WT鼠皮层和海马均为100。注射氯化锂后,KO鼠和WT鼠总GSK3β无明显改变,而KO鼠60 mg/kg,120 mg/kg,200 mg/kg组皮层P-GSK3β表达平均灰度值分别为:147,151,234;海马P-GSK3β分别为108,111,146,较空白组增多;P<0.05。WT鼠用氯化锂后,潜伏期和错误次数以及P-GSK3β表达变化无统计学意义。结论氯化锂能改善KO鼠的学习记忆能力,可能与氯化锂导致的P-GSK3β的表达增加有关,对脆性X综合征基因敲除小鼠有治疗作用。     

Possible interaction of cholinergic and GABAergic systems between MS and CA1 upon memory acquisition in rats

The present study explored the possibility that cholinergic and GABAergic systems of medial septum (MS) might influence acquisition of memory by regulation of acetylcholine (Ach) and γ-aminobutyric acid (GABA) receptors function in hippocampus and vice versa. The step-through passive avoidance (PA) task was used. The results showed that pre-training intra-MS/CA1 administration of nonselective muscarinic Ach antagonist, scopolamine (0.5, 1 and 2μg/rat) and GABA(A) receptor agonist, muscimol (0.01 and 0.02μg/rat) impaired, while acetylcholinesterase inhibitor, physostigmine (0.5 and 1μg/rat) and GABA(A) receptor antagonist, bicuculline (0.25μg/rat) improved memory acquisition. Moreover, intra-CA1/MS administration of a subthreshold dose of muscimol or bicuculline increased and reversed the impairment induced by scopolamine in MS/CA1 respectively (cross injection). Also, the result revealed that, intra-CA1/MS administration subthreshold dose of muscimol reduced improvement of memory induced by physostigmine in the MS/CA1, respectively (cross injection). On the other hand, subthreshold dose of bicuculline in CA1/MS did not alter memory improvement induced by physostigmine in the other site (MS/CA1). In conclusion, both cholinergic and GABAergic systems not only seem to play a role in the modulation of memory in the MS and CA1 but also to have a complex interaction.     

Ascorbic acid supplementation could affect passive avoidance learning and memory in rat

Ascorbic acid (vitamin C) is required for health and, in particular, its supplementation has beneficial effects in some pathological conditions. There are conflicting reports regarding the usefulness of ascorbic acid in the treatment of dementia. In this study, we investigated the effects of acute, short- and long-term pre-training administration of ascorbic acid (60,120 mg/kg) on passive avoidance learning (PAL) and memory in rats. Retention test was done 24 h after training. The results showed that acute injection of ascorbic acid had no significant effect on PAL. On the other hand, both in the short- and long-term ascorbic acid treated groups trials to acquisition were less than control group. Also, ascorbic acid prolonged the step-through latency (STL) and decreased the time spent in the dark compartment in retention test. Thus, it can be concluded that short- and long-term supplementation with ascorbic acid has facilitatory effects on acquisition and retrieval processes of passive avoidance learning and memory in rats.     

Nicotine improves learning and memory in rats: morphological evidence for acetylcholine involvement

It has been suggested that nicotine improves rapid information processing (learning and memory) tasks. However, it is not clear which aspects of cognition actually underlie these improvements because relatively less attention has been given to nicotinic cholinergic systems compared to muscarinic systems. The authors therefore studied the effects of nicotine on the learning and memory performance by a step-through passive avoidance task. Nicotine (0.4 mg/kg) was administered s.c. single dose (acute group), once a day for 3 days (subchronic group) or 21 days (chronic group). Nicotine treated and control rats were trained in one trial learning step-through passive avoidance task, where retention latencies were carried out 1 h, 24 h, and 3 days after learning trial. Treatment with nicotine before training session prolonged the latencies significantly (p < .01). Control group, acute, subacute and chronic nicotine treatment groups showed latencies 4.75 +/- 0.6, 69.4 +/- 14, 116.2 +/- 30, and 118.5 +/- 23 s, respectively. In addition, to prove the actual contribution of nicotinic cholinergic system in improvement of learning and memory processing, histological methods that permit the visualization and quantification of ACh levels were used. Electron microscopic evaluation revealed increased numbers of Ach-containing vesicles especially in hippocampus in chronic nicotine-treated rats; although frontal and temporal cortex in addition to hippocampus showed increment in Ach vesicles in a lesser extent in all nicotine treatment groups. These results indicate that long-term nicotine treatment can be important for improving cognitive function in regard to increased cholinergic activity.     

Brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rat: Efficiency of Sonchus asper

ABSTRACT: BACKGROUND: Sonchus asper (SA) is traditionally used as a folk medicine to treat mental disorders in Pakistan. The aim of this study was to investigate the effect of polyphenolic rich methanolic fraction of SA on cognitive performance, brain antioxidant activities and acetylcholinesterase activity in male rats. METHODS: 30 male Sprague-Dawley rats were equally divided into three groups in this study. Animals of group I (control) received saline (vehicle), group II received SA (50 mg/kg) body weight (b.w.), and group III treated with SA (100 mg/kg b.w.,) orally in dimethyl sulphoxide (DMSO) for 7 days. The effect of SA was checked on rat cognitive performance, brain antioxidatant and acetylcholinesterase activities. Evaluation of learning and memory was assessed by a step-through a passive avoidance test on day 6 after two habituation trials and an initial acquisition trial on day 5. Antioxidant potential was determined by measuring activities of superoxide dismutase (SOD), catalase (CAT), contents of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) in whole-brain homogenates. Acetylcholinesterase (AChE) activity was determined by the colorimetric method. RESULTS: Results showed that 100 mg/kg b.w., SA treated rats exhibited a significant improvement in learning and memory (step-through latency time). SA administration reduced lipid peroxidation products and elevated glutathione levels in the SA100-treated group. Furthermore, salt and detergent soluble AChE activity was significantly decreased in both SA-treated groups. Short-term orally supplementation of SA showed significant cognitive enhancement as well as elevated brain antioxidant enzymes and inhibited AChE activity. CONCLUSION: These findings stress the critical impact of Sonchus asper bioactive components on brain function. KEYWORDS: Sonchus asper, Cognitive performance, Acetylcholinesterase activity, Antioxidant enzymes.     

外源性N-甲基-D-天冬氨酸对成年大鼠被动回避学习记忆的影响

目的 探讨脑内植入外源性N-甲基-D-天冬氨酸(NMDA)对成年大鼠被动回避学习记忆的影响. 方法 在大鼠脑内植入不同浓度的NMDA缓释膜片后,比较各组大鼠被动同避学习记忆(避暗实验)的能力以及额前腹内侧皮质(vMPFC)及扣带同前皮质(ACC)区域NMDA受体活性的区别. 结果 避暗实验中各组大鼠潜伏期和错误次数间差异无统计学意义(P=0.846,P=0.792).各组大鼠vMPFC及ACC区域的NMDA受体活性之间差异无统计学意义(P=0.546),但随着所植入的缓释膜片中NMDA浓度增加.这些区域NMDA受体活性有降低的趋势. 结论 外源性植入NMDA对成年大鼠被动回避学习记忆无明显影响,但本实验为进一步研究NMDA改变受损脑组织的神经可塑性奠定了一定的基础.     

Concurrent muscarinic and beta-adrenergic blockade in rats impairs place-learning in a water maze and retention of inhibitory avoidance

These experiments examined the effects of separate and concurrent muscarinic cholinergic and beta-adrenergic blockade on inhibitory (passive) avoidance performance and spatial learning in the Morris water maze. Pretraining systemic administration of either scopolamine (0.3 or 1.0 mg/kg) or propranolol (3.0 or 10.0 mg/kg) had no significant effect on one-day retention of step-through inhibitory avoidance training. Similarly, pretraining administration of either 0.3 mg/kg scopolamine or 10 mg/kg propranolol did not affect spatial learning in the Morris water maze. However, combined administration of scopolamine and 10.0 mg/kg of propranolol impaired performance on these tasks. These findings further support a role for interactions between norepinephrine and acetylcholine in the modulation of learning and memory and implicate the participation of beta-adrenergic mechanisms in this interaction. Because cholinergic and noradrenergic deterioration is found in aging and Alzheimer's disease, these results also have implications regarding the role of age-related noradrenergic and cholinergic dysfunction in cognitive decline.     

Genomic and nongenomic effects of intrahippocampal microinjection of testosterone on long-term memory in male adult rats

In addition to their well-known genomic effects via intracellular receptors, androgens rapidly alter neuronal excitability through a nongenomic pathway. The nongenomic effect of testosterone, as the main androgen, apart from its traditional effects, was assessed in one of the fundamental centers of learning and memory, the hippocampus, on long-term memory (LTM) in passive avoidance conditioning. Different doses of testosterone enanthate (T) or testosterone-BSA (T-BSA) bilaterally were injected into the CA1 region of the hippocampus 15 min before shock delivery (1 mA during 5 s) in a two-compartment passive avoidance apparatus. After 24 h, animals were tested for passive avoidance retrieval. Bilateral injection of 20 microg T or 55 microg T-BSA into the CA1 significantly decreases step-through latency. Therefore, it seems that testosterone can impair LTM in passive avoidance conditioning both via intracellular receptors and through nongenomic pathway.     

Combined exposure to nicotine and ethanol in adolescent mice differentially affects memory and learning during exposure and withdrawal

Human adolescents often associate tobacco smoking and consumption of alcoholic beverages. In spite of this frequent association, little is known about the basic neurobiology of the dual exposure in the adolescent brain. In the present work, we assessed, through the use of the step-through passive avoidance box (2mA, 2s; test-retest interval of 24h), short- and long-term memory/learning effects of nicotine (NIC) and/or ethanol (ETOH) exposure during adolescence (postnatal days 30-45: PN30-45) in four groups of male and female C57BL/6 mice: (1) concomitant NIC [nicotine free base solution (50microg/ml) in 2% saccharin to drink] and ETOH [ethanol solution (25%, 2g/kg) i.p. injected every other day] exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. During exposure (PN44-45), deficits in memory/learning due to concomitant NIC+ETOH exposure reflected the summation of the two individual sets of effects. During a short-term drug withdrawal (PN49-50), nicotine improved memory/learning, however, ethanol blocked nicotine-induced improvements. One month post-exposure (PN74-75), a significant female-only improvement in memory/learning was observed as a result of co-administration. In conclusion, our results suggest that detrimental effects of nicotine and ethanol on memory/learning during adolescent combined exposure represent a worsened outcome from the dual exposure. However, negative effects of the combined exposure fail to persist during withdrawal. In fact, the combined exposure elicits a sex-dependent late onset beneficial effect on memory/learning during withdrawal.     

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.     

Scopolamine blocks the effects of swim stress on memory retrieval in rats

Summary This study examined whether application of swim stress improved retrieval of a passive avoidance memory and if pretreatment with the anticho-linergic agent, scopolamine, blocked this effect on memory retrieval. Animals initially given a passive avoidance training session were subjected to either a two or four swim stress sessions (15 min each) with or without prior treatment of scopolamine (0.05 or 0.1 mg/kg). The retrieval performance in passive avoidance test and motor activity was assessed 24 hr after the last swim stress session. In an independent control experiment, the passive avoidance training and test were conducted respectively, 24 and 72 hr after the last of four swim stress sessions with or without prior injection of scopolamine (0.1 mg/kg). The results showed an enhanced performance for the passive avoidance task in rats subjected to four swim stress sessions in both experiments and scopolamine given 30 min prior to each stress session diminished this performance of animals in the passive avoidance test. Two swim stress sessions with or without scopolamine treatment caused no significant effects on the retrieval performance. Also, no significant difference was observed among the groups in motor activity following any of the stress treatments in the open field test. These results, thus suggested for the first time, a relationship among swim stress, cholinergic activity and avoidance memory processes.     

The cannabinoid CB1 receptor antagonist rimonabant dose-dependently inhibits memory recall in the passive avoidance task in domestic chicks (Gallus domesticus)

The effect of endocannabinoids on synaptic plasticity has been demonstrated in a variety of species and brain regions. Relatively little is known about the localization and significance of cannabinoid (CB) receptors in the avian brain. The objective of the present study was to investigate the effect of a specific CB₁ receptor antagonist upon the acquisition and consolidation of memory in young domestic chicks. One-day-old domestic chicks (Gallus domesticus) were trained and tested by the passive avoidance paradigm. Systemic (i.p.) administration of the CB₁ receptor antagonist rimonabant in a dose of 1 mg/kg 30 min before the training failed to affect learning, but a similar treatment 30 min before the recall (5.5 h after training) attenuated the retention in 60% of animals. In another set of animals, a dose of 0.01 mg/kg produced no significant impairment, whereas doses 0.1 mg/kg and 1.0 mg/kg resulted in significant attenuation in passive avoidance performance when tested 30 min prior to recall. The results are discussed in terms of a putative mediating role of CB receptors in the consolidation of memory.     

Hypericum extract and hyperforin: memory-enhancing properties in rodents

Effects of a Hypericum extract in therapeutic use and hyperforin sodium salt were evaluated in rat and mouse avoidance tests. In a conditioned avoidance response (CAR) test on the rat, oral daily administration of hyperforin (1.25 mg/kg/day) or of the extract (50 mg/kg/day) before the training sessions considerably improved learning ability from the second day onwards until the day 7. In addition, the memory of the learned responses acquired during 7 consecutive days of administration and training was largely retained even after 9 days without further treatment or training. The observations made using different doses indicate that these learning-facilitating and/or memory-consolidating effects by the agents follow inverse U-shaped dose-response curves in dose ranges lower than (for hyperforin) or equal to (for Hypericum extract) their effective dose in the behavioral despair test for antidepressants. In a passive avoidance response test on the mouse, a single oral dose (1.25 mg/kg) of hyperforin not only improved memory acquisition and consolidation, but also almost completely reversed scopolamine-induced amnesia. The single Hypericum extract dose tested (25 mg/kg) did not reveal any significant effects in the passive avoidance response (PAR) test on the mouse. These observations suggest that the Hypericum extract could be a novel type of antidepressant with memory enhancing properties, and indicate that hyperforin is involved in its cognitive effects. Pure hyperforin seems to be a more potent antidementia agent than an antidepressant.     

Cysteamine-induced depletion of somatostatin produces differential cognitive deficits in rats

The effects of a variety of doses of systemically administered cysteamine (a somatostatin depletor) were studied on step-through passive avoidance retention, as well as acquisition and performance of a delayed spatial alternation task and a signaled extinction discrimination task in rats. Retention of single trial passive avoidance was significantly reduced by a pretraining (60-min) dose of cysteamine at 50, 100, 150 and 200 mg/kg s.c. This effect was shown to be sensitive to behavioral manipulation; in a second experiment, a retention deficit was found only at the two highest doses tested (150 and 200 mg/kg s.c.) after a second exposure to the footshock. In the operant conditioning studies, biweekly injections (Monday and Wednesday) of cysteamine administered one hour before testing produced no statistically significant changes in acquisition or performance of either the delayed spatial alternation or the signaled discrimination task. The results of these series of experiments suggest that active somatostatin release or chronic somatostatin depletion may selectively affect performance maintained by different behavioral procedures.