Passive Avoidance Behavior Research Articles

Effect of Tong Luo Jiu Nao on Aβ-degrading enzymes in AD rat brains

Ethnopharmacological relevance Tong Luo Jiu Nao (TLJN) is a modern Chinese formula based on Traditional Chinese Medicine theory that has been used to treat ischemic cerebral stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanism of the TLJN effect on Alzheimer's disease (AD). Aim of the study To investigate the effect of TLJN on β-amyloid-degrading enzymes and learning and memory in the AD rat brain. Materials and methods AD rats whose disease was induced by Aβ 25–35 injection into the bilateral hippocampus CA1 region were subjected to intragastric administration of various preparations. The experimental animals were healthy male Sprague-Dawley rats which were randomly divided into normal, sham, model, TLJN min, TLJN max and donepezil hydrochloride groups. Spontaneous alternation and passive avoidance behavior, which are regarded as measures of spatial learning and memory, were investigated using Y-maze testing. Western blotting and immunohistochemistry were used to observe the therapeutic effect of TLJN on the deposits of amyloid plaque and on the expression of synaptophysin, insulin-degrading enzyme and neprilysin. Results Y-maze results showed that the AD model group presented with spatial learning and memory impairments. Hematoxylin–eosin and Congo red staining indicated neuronal impairment and deposits of amyloid plaque in the model group and these results were consistent with their learning and memory deficits in the Y-maze. The TLJN-treated groups exhibited prolonged a cavity delitescence, decreased arm entries and improvement in learning and memory. Moreover, the structure of the neurons of the treated groups was restored and the expression of synaptophysin increased in both the hippocampus and cortex. In addition, their levels of insulin-degrading enzyme and neprilysin in the cortex and hippocampus were upregulated and the amyloid plaque was decreased. Conclusion TLJN can improve learning and memory, up-regulate insulin-degrading enzyme and neprilysin levels, promote the degrading of Aβ and clear amyloid plaque from the AD rat brain. In future, TLJN may have significant therapeutic potential in the treatment of AD patients.

Microinjection of l-arginine into corpus callosum cause reduction in myelin concentration and neuroinflammation

Role of nitric oxide (NO) in inflammationary diseases such as multiple sclerosis (MS) has been proposed previously. We sought to examine if NO plays centrally a key role in MS related phenomena; demyelination or neuroinflammation. Female Wistar rats (weighing 200–250 g) were mounted in a stereotaxic apparatus and received injections of l-arginine aimed at corpus callosum (AP: 1.2, L: ± 1.8, V: 3.2). The drug (50–200 μg/rat) was microinjected intra-corpus callosum repeatedly (3–5 times/each per day). Control groups solely received saline (1 μg/rat) into the corpus callosum. The animals were tested for the novelty seeking behavior using the conditioning task. Memory impairment was examined using the shuttle box and Y-maze. l-NAME was pre-injected to l-arginine to involve the NO. All animals' brains were also processed for histological evaluation. l-arginine produced significant changes in the novelty seeking behavior but not in the memory formation, evidenced by passive avoidance and alternation behaviors. Pre-injection of l-NAME reversed the response to l-arginine. Present study further revealed a prominent inflammation as well as myelin elimination in the l-arginine treated rats' brains. These data suggest that the NO infusion in the myelin rich areas such as corpus callosum may lead to MS signs centrally.

Preying on the Misfortune of Others: When Do States Exploit Their Opponents’ Domestic Troubles?

Scholarly work on diversionary war is ubiquitous as is the observation that findings in the literature are mixed. One reason for these mixed results may be that potential targets strategically avoid conflict. Another theoretical possibility is that some types of domestic trouble restrain state leaders’ foreign policy behavior rather than giving them an incentive to use force. These domestic conditions could provide their international opponents with an opportunity to exploit the state’s weakness. If a state interprets its opponent’s domestic context as an opportunity to take advantage of a weakness, then we should anticipate greater aggressiveness rather than the passive avoidance behavior much work on strategic interaction and the use of force suggests. Our heteroskedastic model provides evidence that where some domestic conditions create threats for foreign opponents, others provide opportunities.

Cortico-Thalamic Connectivity is Vulnerable to Nicotine Exposure During Early Postnatal Development through α4/β2/α5 Nicotinic Acetylcholine Receptors

Tobacco smoke exposure during development can result in lasting alterations in sensory processing and attention. This suggests that some constituent of smoke, such as the primary addictive component, nicotine, alters neurodevelopment. Although many effects of developmental nicotine exposure have been identified in humans and animal models, very few mechanistic studies have identified the molecular and anatomical basis for a defined behavioral consequence of developmental exposure. We show in this study that a mouse model of developmental nicotine exposure results in hypersensitive passive avoidance in adulthood. We have used transgenic mice in which β2 subunit containing nicotinic acetylcholine receptors (β2* nAChRs) are expressed exclusively on corticothalamic neurons (β2 tr(CT) mice) to identify the receptor subtypes involved and also to define the circuit level site of action responsible for this persistent, nicotine-induced behavioral phenotype. Further characterization of the native nAChRs expressed in this circuit indicates that both (α4)(2)(β2)(3) and (α4)(2)(β2)(2)α5 nAChR subtypes are present in corticothalamic projections. Consistent with a role for (α4)(2)(β2)(2)α5 nAChRs in mediating the effect of developmental nicotine exposure on adult passive avoidance behavior, constitutive deletion of the α5 nAChR subunit also alters this behavior. A critical period for this developmental consequence of nicotine exposure was defined by limiting exposure to the early post-natal period. Taken together, these studies identify a novel consequence of developmental nicotine exposure in the mouse, define the nAChR subtypes and neural circuit involved in this behavioral change and delimit the neurodevelopmental period critical for vulnerability to a behavioral alteration that persists into adulthood.

Behavioral interactions between a coexisting rodent Micaelamys namaquensis and macroscelid Elephantulus myurus

Abstract A number of mechanisms are known to influence coexistence in small mammal communities. However, the role of behavioral interactions in promoting species coexistence is under-represented in the literature. We studied the behavioral interactions of two coexisting small mammals, the Namaqua rock mouse Micaelamys namaquensis (Rodentia) and the Rock sengi Elephantulus myurus (Macroscelidae), which have high dietary and microhabitat overlap. Using wild-caught individuals, intra- and interspecific dyadic encounters were staged in tanks on a neutral rocky outcrop. Interspecific dyads displayed significantly more active avoidance behavior. There was no support for the prediction that the larger, more specialist species, E. myurus, is behaviorally dominant over M. namaquensis. Intraspecific encounters of E. myurus showed significantly more passive avoidance and amicable behavior, whereas the behavior of M. namaquensis did not differ between intra- and inter-specific encounters, both of which were characterized by low levels of aggression and amicability. Thus, due to the lack of aggression, direct competition appears weak and instead mutual avoidance may reduce or minimize interspecific interactions, potentially promoting coexistence.

3R tau expression modifies behavior in transgenic mice

Tauopathy is a group of disorders characterized by the accumulation of hyperphosphorylated tau protein in the brain, resulting in dementia. Here, tau-related behavior was evaluated in a mouse model with brain overexpression of the shortest human tau isoform (0N3R). Two groups of animals [tau-transgenic (tau-tg) and control littermates] were tested for learning and memory at 1 and 7 months. In the Morris water maze, all mice learned the task at 1 month of age and did not learn at 7 months. In contrast, at 7 months, the tau-tg animals demonstrated better retention of the passive avoidance response compared with their control littermates, which did not learn. In the open field test, no differences were measured between transgenic and nontransgenic young mice, but significantly higher locomotion was observed in the 7-month-old tau-tg mice compared with controls. Behavior during the elevated plus maze test was the same at 1 month, but at 7 months increased entrance to the different arms was observed in the tau-tg group. Tau expression and phosphorylation levels were analyzed at 8 months. In the subcortical brain region associated with passive avoidance behavior, the tau-tg mice demonstrated increased brain tau expression coupled with reduced relative phosphorylation. In contrast, increased tau expression and phosphorylation were measured in the cerebral cortex of the tau-tg mice. In conclusion, 7-8-month-old tau-tg mice overexpressing nonmutated 0N3R human tau isoform demonstrated enhanced behavior in the passive avoidance test, paralleled by relative tau hypophosphorylation in the subcortical brain region.

Behavioral and physiological responses of nestling pied flycatchers to acoustic stress

The extended secretion of stress hormones in fully developed animals is known to have profound consequences. However, little is known about the effects of stress on the behavior and physiology of free-living young animals, and how such responses relate to each other. We repeatedly (during 5 consecutive days, 1 h/day) exposed the nestlings of a passerine bird, the pied flycatcher ( Ficedula hypoleuca), to recordings of nestling distress calls and examined their behavioral and physiological responses to the stressor on the first and the last day of the experiment (on days 9 and 13 post-hatch, respectively). In comparison with control siblings, stressed nestlings reduced the amount of time that they devoted to vocalization and locomotion and increased levels of circulating corticosterone. In 9-day-old nestlings, the level of stress-induced hormone was negatively related to locomotor activity, but not to the rate of vocalizations. The repeated presentation of the stressor increased the heterophile-to-lymphocyte ratio in nestlings but did not affect nestling growth rate. In 13-day-old nestlings, the level of stress-induced corticosterone was not related to behavioral activity. These results suggest that the high level of corticosterone released by immature nestlings in response to a stressor may promote anti-predator behavior (e.g., passive avoidance behavior). Moreover, repeatedly induced stress may have a cumulative and potentially negative effect on individual physiology.

Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.

The effects of Uncaria tomentosa total alkaloid and its oxindole alkaloid components, uncarine E, uncarine C, mitraphylline, rhynchophylline and isorhynchophylline, on the impairment of retention performance caused by amnesic drugs were investigated using a step-down-type passive avoidance test in mice. In this test, the retention performance of animals treated with the amnesic and test drugs before training was assessed 24 h after training. Uncaria tomentosa total alkaloid (10-20 mg kg(-1), i.p.) and the alkaloid components (10-40 mg kg(-1), i.p.), as well as the muscarinic receptor agonist oxotremorine (0.01 mg kg(-1), i.p.), significantly attenuated the deficit in retention performance induced by the muscarinic receptor antagonist scopolamine (3 mg kg(-1), i.p.). The effective doses of uncarine C and mitraphylline were larger than those of other alkaloid components. Uncarine E (20 mg kg(-1), i.p.) also blocked the impairment of passive avoidance performance caused by the nicotinic receptor antagonist mecamylamine (15 mg kg(-1), i.p.) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 7.5 mg kg(-1), i.p.), but it failed to affect the deficit caused by the benzodiazepine receptor agonist diazepam (2 mg kg(-1), i.p.). Rhynchophylline significantly reduced the mecamylamine-induced deficit in passive avoidance behaviour, but it failed to attenuate the effects of CPP and diazepam. These results suggest that Uncaria tomentosa total alkaloids exert a beneficial effect on memory impairment induced by the dysfunction of cholinergic systems in the brain and that the effect of the total alkaloids is partly attributed to the oxindole alkaloids tested. Moreover, these findings raised the possibility that the glutamatergic systems are implicated in the anti-amnesic effect of uncarine E.

Protective effects of pseudoginsenoside-F11 on scopolamine-induced memory impairment in mice and rats.

This study assessed the effects of pseudoginsenoside-F11, a component of Panax quinquefolium L., on scopolamine-impaired memory performance in mice and rats. In the one-trial step-down and step-through passive avoidance tests, although pseudo-ginsenoside-F11 used alone did not affect passive avoidance behaviour in naive mice, the latency of avoidance shortened by intraperitoneal scopolamine (2 mg kg(-1)) was prolonged after intragastric administration of pseudoginsenoside-F11 (2 or 4 mg kg(-1), for five days) in both test systems in mice. In the water-maze test, in mice, the time taken to locate the platform after administration of pseudoginsenoside-F11 was shorter than that after administration of scopolamine (1 mg kg(-1), i.p.). In the two-way active avoidance response test, the latency of avoidance was significantly shorter for the pseudoginsenoside-F11-(1.2 or 2.4 mg kg(-1), i.g. for five days) and scopolamine-treated group than for the group of rats given scopolamine only (2 mg kg(-1), i.p.). The percentage avoidance was also reduced after intraperitoneal injection of scopolamine, but was reversed by administration of pseudo-ginsenoside-F11. These results suggest that pseudoginsenoside-F11 antagonized the memory dysfunction induced by scopolamine. However, the mechanism of the memory facilitative action of pseudoginsenoside-F11 merits further elucidation.

Effect of radio-frequency electromagnetic radiations (RF-EMR) on passive avoidance behaviour and hippocampal morphology in Wistar rats

Introduction. The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR) with the brain is a serious concern of our society.Objective. We evaluated the effect of RF-EMR from mobile phones on passive avoidance behaviour and hippocampal morphology in rats.Materials and methods. Healthy male albino Wistar rats were exposed to RF-EMR by giving 50 missed calls (within 1 hour) per day for 4 weeks, keeping a GSM (0.9 GHz/1.8 GHz) mobile phone in vibratory mode (no ring tone) in the cage. After the experimental period, passive avoidance behaviour and hippocampal morphology were studied.Results. Passive avoidance behaviour was significantly affected in mobile phone RF-EMR-exposed rats demonstrated as shorter entrance latency to the dark compartment when compared to the control rats. Marked morphological changes were also observed in the CA3 region of the hippocampus of the mobile phone-exposed rats in comparison to the control rats.Conclusion. Mobile phone RF-EMR exposure significantly altered the passive avoidance behaviour and hippocampal morphology in rats.

Correlations between angiotensinase activity asymmetries in the brain and paw preference in rats

The function of angiotensin peptides is dependent upon the action of several aminopeptidases (APs) termed angiotensinases. Soluble (SOL) and membrane (MEM)-bound alanyl-AP (AlaAP) and cystinyl-AP (CysAP) are involved in the metabolism of angiotensins and related to the modulation of behavior and memory. To study the interactions between angiotensinase activity in the hippocampus and behavioral lateralization, Wistar rats were selected on the basis of their performance in the paw preference test (left-handed, ambidextrous and right-handed) and the activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP were measured in the both hippocampuses. We observed that: (1) the left hippocampus had higher activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP than the right hippocampus; (2) rats showed significant differences in the activities of SOL-AlaAP/CysAP and MEM-AlaAP/CysAP in the hippocampus depending on the behavioral lateralization detecting by paw preference; (3) in three groups of rats, hemispheric dominance - %R/T [%R/T=right hemisphere/(right hemisphere+left hemisphere)x100] activities of MEM-AlaAP, SOL-CysAP and MEM-CysAP was significantly different whereby %RT was lower in left-handed, higher in ambidextrous and intermediate in right-handed rats; (4) individual %R/T activities of SOL-CysAP and MEM-CysAP in the hippocampus were positively correlated with paw preference scores. Finally, we used the passive avoidance behavior test to demonstrate the differences of long-term memory among the three groups. These results suggested that the asymmetric activity of angiotensinase in the rat hippocampus may be associated with both the direction and the intensity of behavioral lateralization as expressed by paw preference.

The Ameliorating Effects of Luteolin on Beta-Amyloid-Induced Impairment of Water Maze Performance and Passive Avoidance in Rats

The present study investigated the effects of luteolin on Abeta (1-40)-induced impairment of Morris water maze (MWM) spatial performance, reference memory, and passive avoidance (PA) behavior in rats. Luteolin treatment was started 4 days before the initiation of behavioral testing (passive avoidance on treatment day of 4-5; MWM spatial performance memory testing on treatment day of 5-7 and MWM reference memory testing on treatment day of 7) and continued until the end of the study. We also measured the activity of Mn-SOD, copper/zinc (Cu/Zn)-SOD and glutathione (GSH) levels in rat cortex and hippocampus to understand the ameliorating effect of luteolin on Abeta (1-40) induced memory impairment. The present results showed that luteolin (5, 10 mg/kg) has a protective effect on Abeta (1-40)-induced memory dysfunction in spatial performance, reference memory, and inhibitory avoidance response impairment. Finally, luteolin also increases the level of Mn-SOD, (Cu/Zn)-SOD and glutathione (GSH) in the cortex and hippocampus to reduce the oxidative stress by Abeta (1-40). Taken together, the results in this study suggest that luteolin (5, 10 mg/kg) treatment improves the learning and memory in Abeta (1-40)-induced cognition deficit in rats. The ameliorating mechanisms of luteolin on Abeta (1-40)-induced amnesia may be related to activating the anti-oxidation system.

Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies

Dimethylaminoethanol pyroglutamate (DMAE p-Glu) is a compound resulting from the reaction between dimethylaminoethanol (an indirect precursor of acetylcholine) and pyroglutamic acid (a cyclic derivative of glutamic acid having procholinergic properties and promnesic effects in both animals and man). The present study undertook preclinical and clinical evaluations to test a potential therapeutic utility for DMAE p-Glu in cognitive impairments related to central cholinergic deficit. In preclinical study, DMAE p-Glu was studied in rats by intracerebral microdialysis in conscious freely moving animals, on performance of rats in the Morris water maze test of spatial memory, and on the deficit in passive avoidance behavior induced by scopolamine. The clinical study examined the effect of DMAE p-Glu on cognitive deficits induced by an intravenous injection of scopolamine in healthy young male subjects. In rat experiments, DMAE p-Glu increased the extracellular levels of choline and acetylcholine in the medial prefrontal cortex, as assessed by intracerebral microdialysis, improved performance in a test of spatial memory, and reduced scopolamine-induced memory deficit in passive avoidance behavior. Clinical study results show that scopolamine induced a memory deficit and that DMAE p-Glu produced a significant positive effect on scores in the Buschke test, as well as a slight but significant difference on choice reaction time. These results indicate that DMAE p-Glu reduces the deleterious effect of scopolamine on long-term memory in healthy volunteers and suggest that DMAE p-Glu might be effective in reducing memory deficits in patients with cognitive impairment.

Effects of the LHRH antagonist Cetrorelix on affective and cognitive functions in rats

The decapeptide LHRH antagonist, Cetrorelix, inhibits gonadotropin and sex-steroid secretion. Cetrorelix is used for IVF-ET procedures and for the treatment of benign prostatic hyperplasia, endometriosis and leiomyomas. However little is known about the effects of Cetrorelix on brain functions. Previously we have tested Cetrorelix in mice on the impairment of the consolidation of a passive avoidance behavior caused by beta-amyloid 25–35, anxiolytic action in the plus-maze, antidepressive action in a forced swimming test, tail suspension and open-field behavior following its administration into the lateral brain ventricle. In the present study we repeated and extended the experiments in rats in order to determine whether there are species differences in the action of Cetrorelix between mice and rats. The effects of Cetrorelix evaluated included the methods used in mice without tail suspension test and extended by measuring core temperature. Cetrorelix fully blocked the impairment of the consolidation of passive avoidance learning when given icv 30 min following administration of beta-amyloid 25–35. If beta-amyloid 25–35 and Cetrorelix were given simultaneously, Cetrorelix was ineffective. Cetrorelix elicited slight anxiogenic and stronger anxiolytic action in the plus-maze, depending on the dose used. In the forced swimming tests, Cetrorelix showed antidepressive-like action. In open-field behavior tests Cetrorelix displayed a U-type action on locomotion with 0.5 and 2 µg increasing locomotion, and increase rearing but and had no effect on grooming at 0.5–2 µg. Cetrorelix had no action on core temperature. Our findings demonstrate that Cetrorelix is able to correct the impairment of the memory consolidation caused by beta-amyloid 25–35. Cetrorelix elicits anxiolytic and antidepressive action, slightly increases locomotion and rearing in open field, but it does not influence the core temperature. The results obtained in rats are similar to those reported previously by us in mice. Collectively our findings confirm the effects of Cetrorelix on brain function in two species and suggest the possible merit of a clinical trial with Cetrorelix in patients with anxiety, depression and Alzheimer's disease.

Fustin flavonoid attenuates β‐amyloid (1–42)‐induced learning impairment

Natural flavonoids ameliorate amyloid-beta peptide (Abeta)-induced neurotoxicity. We examined whether the fustin flavonoid affects Abeta-induced learning impairment in mice. Repeated treatment with fustin significantly attenuated Abeta (1-42)-induced conditioned fear and passive avoidance behaviors. This effect was comparable to that of EGb761, a standard extract of ginkgo. Fustin treatment significantly prevented decreases in acetylcholine (ACh) levels, choline acetyltransferase (ChAT) activity, and ChAT gene expression induced by Abeta (1-42). Fustin also consistently suppressed increases in acetyl cholinesterase (AChE) activity and AChE gene expression induced by Abeta (1-42). In addition, fustin significantly attenuated Abeta (1-42)-induced selective decreases in muscarinic M1 receptor gene expression and muscarinic M1 receptor binding activity (as determined by [(3)H]pirenzepine binding) by modulating extracellular signal-regulated kinase 1/2 (ERK 1/2) and cAMP response-element binding protein (CREB) phosphorylation and brain-derived neurotrophic factor (BDNF) expression. These effects of fustin were reversed by treatment with dicyclomine, a muscarinic M1 receptor antagonist, and SL327, a selective ERK inhibitor, but not by chelerythrine, a pan-protein kinase C (PKC) inhibitor. Taken together, our results suggest that fustin attenuates Abeta (1-42)-impaired learning, and that the ERK/CREB/BDNF pathway is important for the M1 receptor-mediated cognition-enhancing effects of fustin.

Subchronic stress-induced depressive behavior in ovariectomized mice

Aims Mood disorders including depression are more common in women than men, particularly in times of lower estradiol levels. In this study, we investigated the effect of estrogen on emotional behavior in mice in a stress environment. Main methods Female mice were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham mice was kept in a normal environment and the other groups were assigned to a daily stress (1 h/day) for 7 days from 5 days after operation. On the 14th day after operation, subjects were measured to assess behavioral specificity, locomotor activity, elevated plus-maze (EPM) behavior, passive avoidance (PA) behavior and forced swimming behavior. Key findings The OVX plus stress (OVX + S) group showed a significant prolongation of immobility compared with the other groups. In all the groups there were no changes in locomotor activity, EPM behavior or PA behavior. We further examined the effect of estrogen against depressive behavior in the OVX + S group. The vehicle or 17β-estradiol (E2) was administered s.c. to OVX + S mice for 4 days beginning on post-operative day 11. Subchronic E2 treatment decreased the stress response and improved depressive behavior relative to the vehicle group. Significance These data have important implications regarding the prevention of depression in postmenopausal women undergoing estrogen therapy.

Dopamine D4 receptor antagonist L745,870 abolishes cognitive effects of intracerebroventricular angiotensin IV and des-Phe 6-Ang IV in rats

In this study effect of L745,870, a selective D 4 dopamine (DA) receptor blocker, on the pro-cognitive action of intracerebroventricularly (icv) injected angiotensin IV (Ang IV) and des-Phe 6-Ang IV was examined. Male Wistar rats weighing 180–200 g were used. Both peptides given at the dose of 1 nmol facilitated recall of a passive avoidance (PA) behaviour, improved object recognition (OR) memory, decreased number of errors, increased number of sequential correct entries and shortened time-to-goal in an eight-arm radial maze (RM). In the auxiliary tests performed to control for the participation of unspecific motor (open field, OF) and emotional (‘plus’ maze, PM) effects of our treatment in the results of memory tests they had either no (OF) or negligible (PM) effects. Intraperitoneal pretreatment of the animals with 1 mg/kg of L745,870 abolished effects of both peptides on PA and OR and slightly diminished those observed in the eight-arm RM.

Serotoninergic mechanisms of the effects of neurotensin on passive avoidance behavior in rats

The aim of the present work was to identify the features of the actions of neurotensin on administration into the substantia nigra or dorsal cervical nucleus on the reproduction of passive avoidance reactions in rats. The results showed that the action of neurotensin administered into the substantia nigra was accompanied by sharp reductions in passive avoidance reactions, while administration into the dorsal cervical nucleus, conversely, led to increases in these reactions and slowing of their extinction. The effects of microinjections of the serotonin 5-HT(1A) receptor agonist 8-hydroxydipropylaminotetraline (8-OH-DPAT) into these brain structures were analogous to the effects of neurotensin. The different behavioral effects of administration of neurotensin corresponded to identifiable changes in the levels of serotonin and its metabolite 5-hydroxyindoleacetic acid in the caudate nuclei of the brain. These data led to the conclusion that the effects of neurotensin on passive avoidance behavior are associated with the regulation of the emotional state of the animals via actions on the functions of brain serotoninergic structures.

Effect of D3 dopamine receptors blockade on the cognitive effects of angiotensin IV in rats

Our previous studies showed that D(1) and D(2) dopamine receptors are indispensable for the cognitive effects of angiotensin IV (Ang IV) and its des-Phe(6) derivative des-Phe(6)-Ang IV to occur. As most neuroleptics currently used in the treatment of schizophrenia have variable D(2)/D(3) dopaminolytic selectivity, in this study we searched for the role of the D(3) dopamine receptors in facilitating learning and improving memory actions of Ang IV and des-Phe(6)-Ang IV in rats. For this purpose, we evaluated the recall of the passive avoidance (PA) behaviour, object recognition (OR) memory, and the spatial working memory (WM) in rats treated with the intraperitoneal (i.p.) nafadotride (N[(n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide), a highly selective D(3) receptor blocker and then by an intracerebroventricular (i.c.v.) Ang IV or des-Phe(6)-Ang IV. Separate groups of rats receiving the same treatments were run to check for the possible participation of unspecific motor (open field) or emotioned (elevated "plus" maze) effects of our treatments in the results of the cognitive tests. The results revealed Ang IV to express its improving recall of PA, OR memory and WM action roughly similarly in all groups showing only minor or null significance of the D(3) receptors blockade. Interestingly, in the nafadotride pretreated rats, des-Phe(6)-Ang IV beneficial effect on the recall of the PA was weaker than that of Ang IV. Improvement of the spatial WM in an eight-arm radial maze, similar after Ang IV and des-Phe(6)-Ang IV, was not significantly affected by nafadotride. There were no motor and only minor anxiogenic effects of Ang IV and des-Phe(6)-Ang IV abolished by nafadotride in the former case. In conclusion, this study points to the minor significance of the D(3) dopamine receptors in the cognitive effects of Ang IV and to the interesting, though unexplained, inhibition by nafadotride of the des-Phe(6)-Ang IV effects.

Oral THC produces minimal behavioral alterations in preadolescent rats

Although the oral route has traditionally been used for THC administration during the perinatal period in the rat, most studies administering THC during the postnatal period utilize intraperitoneal (ip) administration. In an effort to utilize the same route of administration in both prenatal and postnatal studies, we administered Δ-9-tetrahydrocannabinol (THC) in sesame oil by gavage during postnatal days 22–40 (equivalent to childhood to early adolescence) to male and female rats. We quantified behavior 40 min after administration in the Accuscan activity monitor on days 22, 29 and 40. In addition, we examined active and passive avoidance behaviors in treated adults. Acutely, THC had subtle effects on activity when measured during the period of drug administration and minimal effects on avoidance behaviors examined up to 140 days of age. Since several groups have found that lower doses of THC administered intraperitoneally to periadolescent rats do produce behavioral alterations, we suspect that the inordinately slow absorption of the drug via the oral route may be responsible for the paucity of significant findings in our study. Therefore, oral administration of THC, particularly under conditions of mild food deprivation, may lead to sub-psychoactive concentrations of the drug within the brain.