Effects of posttraining epinephrine injections on retention of avoidance training in mice

Sixty depressed nonschizophrenic patients were admitted to a research unit. Following one drug-free week and one week of placebo, patients received 3.5 mg/kg of imipramine hydrochloride for 28 days. Plasma levels of imipramine and its metabolite desipramine hydrochloride (desmethylimipramine) were measured three times weekly and the relationship between plasma steady-state levels and clinical outcome was examined. Steady-state levels ranged from 50 to 1,050 ng/ml. There was a statistically and clinically significant relationship between plasma levels and response. The relationship existed across the entire sample, and was accentuated when the bipolar and unipolar nondelusional populations were examined. Because a strong relationship between sex and outcome was observed, the unipolar nondelusional patients were stratified by sex and a significant relationship still persisted. Only the unipolar delusional patients failed to demonstrate an association between blood level and clinical response.     

Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.

Previous findings indicate that the memory-impairing effects of posttraining amygdala lesions are attenuated by increasing the number of training trials given prior to the induction of the lesion. The aim of this experiment was to determine whether the degree of impairment is also influenced by the footshock intensity used during training. Rats were given 1 trial of inhibitory avoidance (IA) training with either no footshock or a footshock at 1 of 3 intensities. Sham or neurotoxic amygdala lesions were induced 1 week later. On a retention test performed 4 days after surgery, the performance of all amygdala-lesioned rats given footshock training, including those given the lowest training footshock, was better than that of amygdala-lesioned rats given no training footshock. These findings of preserved retention of IA learning in rats given posttraining amygdala lesions do not support a general hypothesis that the amygdala is a locus of permanent changes underlying aversively motivated learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pre- and posttraining infusion of N-methyl-D-aspartate receptor antagonists into the amygdala impair memory in an inhibitory avoidance task

Involvement of amygdaloid N-methyl-D-aspartate (NMDA) receptors in memory processes was investigated. Rats with cannulas implanted in the basolateral amygdala were trained on a 1 trial step-through inhibitory avoidance task and tested for 24-hr retention. Pretraining infusion of 2-amino-5-phosphonovaleric acid (APV) into the amygdala, but not striatum or hippocampus, produced a dose-dependent retention deficit, which was attenuated by immediate posttraining intra-amygdala infusion of NMDA. Posttraining APV infusion also caused a dose- and time-dependent retention deficit. Pretest APV infusion had no effect on performance in the retention test. Further, pre- or posttraining infusion of 5.0 micrograms APV failed to affect acquisition and retention in the Morris water maze task. These findings suggest that amygdala NMDA receptors are normally activated by aversive training and play a critical role in memory formation for affective experience.     

Effects of cholinergic agonists and antagonists on self-stimulation behavior in the rat.

Trained 23 male Wistar albino rats to press a bar for electrical stimulation of the brain on a 30-sec variable-interval schedule. Ss were tested weekly with 1 or more of the following drugs: physostigmine (50-400 MUg/kg), neostigmine (25-200 MUg/kg), atropine (2-16 mg/kg), methylatropine (2-16 mg/kg), scopolamine (400-1,600 MUg/kg), pilocarpine (500-4,000 MUg/kg), nicotine (100-800 MUg/kg), mecamylamine (1 mg/kg), and methamphetamine (500 MUg/kg). Results support the suggestion that the cholinergic system is composed of 2 reciprocally related components: (a) a muscarinic "no-go" portion, whose activation has an inhibitory effect on self-stimulation; and (b) a nicotinic "go" portion, whose excitatory effect on self-stimulation is (most probably) mediated by norepinephrine. (33 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of pretraining inactivation of the right or left amygdala on retention of inhibitory avoidance training.

Rats with bilateral cannulas aimed at the amygdalae received bilateral infusions of either buffer or lidocaine hydrochloride, or unilateral infusions of each, 5 min before continuous multiple-trial inhibitory avoidance (CMIA) training. Retention was tested 48 hr later. Some of the rats were retrained at this time and tested again 48 hr later. Bilateral infusions of lidocaine prior to the initial training impaired acquisition, retention, and relearning of the CMIA task. Unilateral infusions of lidocaine into the right or left amygdala did not affect acquisition. Rats given lidocaine into the right amygdala were impaired on retention 48 hr later. The findings are consistent with others indicating involvement of the amygdalae in acquisition and consolidation of aversively motivated learning and suggest possible differential involvement of the right and left amygdalae in memory consolidation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of posttraining damage to the pedunculopontine tegmental nucleus on conditioned stimulus transfer in two-way active avoidance in rats.

The effects of posttraining excitotoxic lesions of the pedunculopontine tegmental nucleus (PPTg) on two-way active avoidance after changing the conditioned stimulus (CS) used during prelesion training were examined. Prelesion training was carried out with either a tone or a light as the CS, and this CS was changed during postlesion training. Replacing the tone with a light reduced the performance of control and lesioned rats, but the degree of reduction was higher in the latter. Replacing the light with a tone had slight detrimental effects in lesioned rats but not in controls. Thus, posttraining PPTg lesions slowed down the reacquisition of shuttle-box avoidance under conditions of CS transfer, an effect that may be attributable to disruption of attention and/or gating of sensory stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of scopolamine on activity and passive avoidance learning in rats of different ages.

A total of 320 albino CFE Sprague-Dawley rats aged 16-17, 20-21, 24-25, 28-29, and 70-85 days old were injected intraperitoneally with either scopolamine hydrobromide (SCOP-HBr) or scopolamine methylnitrate (SCOP-Me-NO-3) at 4 levels (0, .5, 1.9, or 2.0 mg/kg. The SCOP-HBr but not he SCOP-Me-NO-3 disrupted passive avoidance in Ss aged 20-28 days. A subsequent replication at higher doses (4.0, 8.0, and 16.0 mg/kg) with 56 70-84 day old adults and 64 16-day-old pups indicated that SCOP-HBr could disrupt passive avoidance in the adults but not in the pups. Results are consistent with the hypothesis that a cholinergic inhibitory system which mediates passive avoidance develops in the rat 16-20 days postnatally. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Corticosterone and avoidance in rats with basolateral amygdala lesions.

Produced deficient acquisition of 2-way active and passive avoidance in 15 male Moll-Wistar rats after bilateral electrolytic lesions restricted to the dorsal part of the basolateral nuclei. Other deficits also suggest a general reduction in fear or arousal: less immobility in the open field and during active-avoidance intertrial intervals, and slower escape latencies and less pituitary-adrenal activation during the initial active-avoidance session. Anatomical analysis of the areas producing the greatest deficit suggests that differential involvement of the insula may explain phylogenetic differences between these data from the rat and previous data from the cat, which show only active-avoidance deficiency after basolateral lesions. (26 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of cycloheximide administered in conjunction with nicotine on retention of a passive avoidance task in mice.

Studied retention of a passive avoidance task in mice given either cycloheximide (30 mg/kg or 100 mg/kg sc) or cycloheximide in combination with nicotine (1.0 mg/kg, ip). Two similar experiments were conducted: In the 1st experiment, the effects of these drugs were studied in 45 inbred C57Bl/6J mice. In the 2nd experiment, the effects of these drugs were studied in 113 genetically heterogenous mice. Cycloheximide was found to have a deleterious effect on retention of the passive avoidance task. Larger doses of cycloheximide were found to be necessary to disrupt memory in heterogenous than C57Bl/6J Ss. Nicotine, when administered in conjunction with cycloheximide, abolished the memory disruptive effects of cycloheximide. Results are discussed in terms of a time-dependent consolidation model of memory storage. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of posttraining administration of insulin on retention of a habituation response in mice: participation of a central cholinergic mechanism

Male Swiss mice were allowed to explore a novel environment, provided by an open-field activity chamber for a 10-min period. The procedure was repeated twice within a 24-h interval. The difference in the exploratory activity between the first (training) and the second exposure (testing) to the chamber was taken as an index of retention of this habituation task. Posttraining intraperitoneal administration of insulin (8, 20, or 80 IU/kg) impaired retention in a dose-related manner, although only the dose of 20 IU/kg of insulin produced significant effects. Thus, the dose-response curve adopted a U-shaped form. Insulin (20 IU/kg) given to untrained mice did not modify their exploratory performance when recorded 24 h later. The effects of insulin on retention were time dependent, suggesting an action on memory storage. An ineffective dose (8 IU/kg) of insulin given together with an ineffective dose of a central acting muscarinic cholinergic antagonist atropine (0.5 mg/kg) or with a central acting nicotinic cholinergic antagonist mecamylamine (5 mg/kg) interacted to impair retention. In contrast, neither methylatropine (0.5 mg/kg), a peripherally acting muscarinic receptor blocker, nor hexamethonium (5 mg/kg), a peripherally acting nicotinic receptor blocker, interacted with the subeffective dose of insulin on retention. The impairing effects of insulin (20 IU/kg) on retention were reversed by the simultaneous administration of physostigmine (70 microg/kg) but not neostigmine (70 microg/kg). We suggest that insulin impairs memory storage of one form of learning elicited by stimuli repeatedly presented without reinforcement, probably through a decrement of brain acetylcholine synthesis.     

Effects of amygdaloid lesions on the performance of rats in four passive avoidance tasks

The blocking effect of apomorphine on the rise in striatal dopamine (DA) content, induced by 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) was taken as a measure for the intrastriatal feedback inhibition of DA synthesis. The effects of cholinergic drugs on this feedback system were assessed in order to verify the hypothesis that this mechanism is mediated via an intrastriatal cholinergic link. We presumed that DA receptors were located on a cholinergic neuron, while the cholinergic terminals in turn made direct or indirect axon-axonal contact with the dopaminergic nigro-striatal pathway (N.S.P.). Although cholinergic agents could modify the effect of HA-966 on striatal DA content, it proved to be impossible to counteract the blocking effect of apomorphine with cholinergic drugs as was to be expected. Therefore we concluded that the effect of apomorphine was not brought about in the way which had been postulated.     

Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats.

Rats were submitted to a training and a test session in a shuttle avoidance task. In some groups, a second training session was interpolated 2 or 24 hr after the first session. In others, a session of extinction was interpolated 2 or 24 hr after the training session. When the interpolated task was 2 hr after training, training-test interval was 24 hr. When the interpolated task was 24 hr after training, training-test interval was 48 hr. The additional training enhanced, and the extinction depressed, retention test performance. Diazepam, given 30 min prior to the first (or only) training session enhanced the performance of avoidance responses in that session but inhibited it in the subsequent retention test. Diazepam given 90 min after training had no effect on retention. Diazepam given 30 min prior to either the additional training session or the extinction session did not affect performance in that session but canceled their effects on retention test performance. The effects are related to the previously described prevention by diazepam of interfering effects on memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of varying active/passive shock levels in shuttle box avoidance in rats.

Ran 60 male Sprague-Dawley albino rats in a shuttle box with 3 levels of shock intensity-high (H), medium (M), and low (L)-which varied independently on each side. This yielded 6 groups defined by the shock level in the 2 chambers: H-H, M-M, L-L, H-L, H-M, M-L. Results indicate that when active shock level was held constant, avoidance behavior was a function of passive shock level, with lower passive shock level producing higher levels of avoidance. Avoidance was not a function of active shock level when passive shock level was held constant. 10 controls were run using a unidirectional paradigm, and avoidance was not found to be a function of the active shock level. Results are interpreted as emphasizing the role of passive avoidance in bidirectional shuttling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining norepinephrine infusion into the central amygdala differentially enhances later retention in Roman high-avoidance and low-avoidance rats.

Memory-enhancement effects of norepinephrine (NE) were investigated by infusing NE into the central amygdala (CEA) of Roman high-avoidance (RHA) and low-avoidance (RLA) rats after training on active and passive behaviors in the defensive-burying paradigm. During acquisition, both lines spent comparable time in burying behavior. RLA rats, but not RHA rats, also displayed substantial immobility. During retention, the CSF-treated RLA rats mostly displayed immobility to the nonelectrified probe, whereas the RHA rats showed neither burying nor immobility. In the RLA rats, high-dose (200 ng), but not low-dose (20 ng), NE infusion enhanced the duration of the passive response (immobility) without affecting the active response. NE given into the CEA of RHA rats caused a selective dose-dependent appearance of the active behavioral component. The results suggest a phenotype-dependent effect of intra-amygdaloid NE on memory processes in the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased training in an aversively motivated task attenuates the memory-impairing effects of posttraining N-methyl-D-aspartate-induced amygdala lesions.

Examined the effect of variations in the amount of preoperative training on the retention deficit produced by posttraining lesions of the amygdaloid complex (AC). Rats received 1, 10, or 20 training trials in a footshock-motivated retention escape task 7 days before receiving N-methyl-{d}-aspartate (NMDA) lesions of the AC. Inhibitory avoidance retention performance, which was measured 4 days postoperatively, indicated that increased training improved retention in AC-lesioned animals as well as in control animals. The retention performance of AC-lesioned animals was impaired when compared with that of controls; however, the impairment was partially attenuated by increased preoperative training. The finding that AC-lesioned animals displayed greater locomotor activity on the retention test compared with nonlesioned controls suggests that the increased activity may have contributed to the impaired inhibitory avoidance retention performance. Two days after the retention test, some of the AC-lesioned animals were subsequently trained on a continuous multiple-trial inhibitory avoidance response in the same apparatus. AC lesions did not block acquisition or retention of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploration and avoidance in rats with lesions in amygdala and piriform cortex.

Lesions localized to specific areas of the amygdala and overlying cortex in 41 adult male M?ll-Wistar rats produced differential effects in several behavioral tasks. Three different types of lesions were tested: central, basolateral, and cortex lateral to the amygdala. Lesions restricted to the central nucleus produced increased activity on all parameters studied in an open-field test, but the other 2 groups were not changed. In 1-way active avoidance all 3 groups with lesions showed deficits. The most pronounced change was observed in the central group. All groups showed the same degree of retention loss, but in forced extinction of 1-way active avoidance after retraining, the cortical and basolateral groups were most defective. A fear-reduction hypothesis is proposed for the central lesion. The basolateral and cortical areas may be more specifically involved in passive avoidance behavior. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic lesion of the striatum impairs acquisition and retention of a passive avoidance response.

Significant impairments in the acquisition and retention of a step-down passive avoidance task were found in Sprague-Dawley rats with striatal lesions induced by the cholinergic neurotoxin AF64A. No significant differences between control and AF64A-injected Ss were found in sensitivity to electric shock or in various measures of spontaneous locomotor activity. Striatal choline acetyltransferase (CAT) activity was significantly decreased in AF64A-treated Ss compared to controls, whereas glutamic acid decarboxylase (GAD) activities were not. Furthermore, there were no significant differences between groups in CAT and GAD in either the cortex or the hippocampus, supporting the specificity of the lesion to the striatum. The passive avoidance deficits support a role for the striatal cholinergic system in complex behavioral processes. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scopolamine's effect on passive avoidance behavior in immature rats

Male albion rats ranging in age from 15-30 days were injected with either scopolamine hydorbromide or saline, prior to training and retention testing on a black-white passive avoidance (PA) task. Pretraining administration of a 1.0-mg/kg dose of scopolamine significantly increased the median number of trails to criterion for 18-, 21-, and 30-day-old rat pups when compared with their saline controls. Fifteen-day-olds showed drug-related PA deficits when a 2.0-mg/kg dose was given. Retention data reflect characteristic age-dependent memory loss over the 1-week acquistionretention period with no apparent state-dependent effects. The data suggest the presence of cholinergic inhibitory mediation of PA responding in preweanling and postweanling pups.     

Chloramphenicol-induced amnesia for passive avoidance training in the day-old chick

In all, 56 triads of same-sex 3rd-, 4th-, and 5th-grade children were observed during an intimate discussion, a cooperative puzzle task, a competitive game, and free play. Observers coded triadic interaction using a Q sort and individual process ratings. Of particular interest was how gender and the pattern of friendship ties among group members related to children's behavior. Triads of girls were more intimate, exchanged more information, and were less aggressive than were triads of boys. Analyses of within-gender variability revealed 2 prototypical types of triads among boys but only 1 among girls. Girls and boys expressed similar attitudes toward triadic interaction in postsession interviews. However, girls', but not boys', attitudes were closely linked to the quality of interactions during the session. For both sexes, interaction was not strongly influenced by the initial configuration of friendship ties among triad members.