mediately after acquisition (7) and lasts sev- eral hours (6-9). It coexists with, but is not dependent upon, short-term memory pro- cesses, which operate through biochemical systems of their own (10-12). It relies on a sequence of biochemical events in the CA1 region that are very similar to those underly- ing long-term potentiation (LTP) in that same region (13). Long-term memory consolida- tion of inhibitoryavoidance begins by acti- vation of N-methyl-D-aspartate (NMDA), D,L- a-amino-3-hydroxy-5-methyl-4-isoxal- one propionate (AMPA) and metabotropic glutamate receptors (3,6,14), followed by activation of calcium-calmodulin dependent protein kinase II (CaMKII) (5,15-17), pro- tein kinase C (PKC) (6) and mitogen-acti- vated protein kinase kinase (MAPKK) (12,18), and by an early peak of protein kinase A (PKA) activity and increased levels of nuclear phosphorylated cAMP response element binding protein (P-CREB) (8,11), among other events (6). The chain of events culminates at 3-6 h with a second peak of activation of the cAMP/PKA/P-CREB sig- naling pathway (6,8,19). Both PKA/P-CREB peaks are regulated by dopamine D 1 recep- tors (10,20,21). Some of these molecular steps also take place in the entorhinal cortex and other brain regions (6,20).
to test. Consistent with previous findings (5,7,8), intra-amygdala CNQX attenuated, but did not block, inhibitoryavoidance re- tention when given 10 min prior to test. This indicates that amygdaloid non-NMDA re- ceptors are involved in retrieval of that task. However, the finding that additional training prevented the effect of CNQX suggests that non-NMDA receptor activation in the amyg- dala is not a critical mechanism of retrieval, and that the amygdala is not a critical site of storage and retrieval of fear-motivated memory. This is consistent with previous evidence that increased training attenuates the impairing effects of amygdaloid lesions (14) and intra-amygdala CNQX (15) on an aversively motivated escape training re- sponse.
The demonstration of an aggravating ef- fect of MRN lesion on post-training scopola- mine-induced working memory storage defi- cit is consistent with many reports. For in- stance, 5,7-dihydroxytryptamine injections into the fimbria-fornix that prevent 5-HT influence originating from the MRN, in com- bination with median septum lesions, pro- duce deeper memory deficits than those in- duced by median septum lesion alone (8,9). Pre-training p-chloroamphetamine adminis- tration to produce 5-HT depletion in the midbrain, which by itself has no effect, po- tentiates the disruptive effects of scopola- mine when given immediately after training (31). All arguments presented indicate a clear synergistic interaction between serotonergic and muscarinic AChergic systems in the regu- lation of storing performance of working memory in the inhibitoryavoidance.
It has been postulated that the amnestic effects of intra-amygdala infusions of AP5 are related to a blockade of neural plasticity processes such as NMDA-dependent long- term potentiation (LTP) at amygdaloid glu- tamatergic synapses (2,5,6,10,13,14). In sup- port of this view, it was recently shown that fear conditioning induces LTP-like changes in auditory-evoked potentials in the lateral nucleus of the amygdala, suggesting a role for LTP in the amygdala in fear memory (14). However, extensive evidence suggests that the amygdala is a modulatory site which regulates memory storage and/or consolida- tion in other brain regions, rather than a critical site for plasticity underlying memory acquisition and storage (1,3,16-20). This view is supported by studies showing that amygda- loid lesions do not block contextual fear conditioning (20) and retention of inhibitoryavoidance (16). Moreover, overtraining can attenuate the amnestic effects of amygdaloid lesions (18), intra-amygdala infusions of NMDA receptor antagonists (9) and intra- amygdala infusions of the non-NMDA re- ceptor antagonist 6-cyano-7-nitroquinoxa- line-2,3-dione (CNQX) (17,19).
The deleterious effects of paradoxical sleep deprivation (SD) on memory processes are well documented. Physical exercise improves many aspects of brain functions and induces neuroprotection. In the present study, we investigated the inﬂuence of 4 weeks of treadmill aerobic exercise on both long-term memory and the expression of synaptic proteins (GAP-43, synapsin I, synaptophysin, and PSD-95) in normal and sleep-deprived rats. Adult Wistar rats were subjected to 4 weeks of treadmill exercise training for 35 min, ﬁve times per week. Twenty-four hours after the last exercise session, the rats were sleep-deprived for 96 h using the modiﬁed multiple platform method. To assess memory after SD, all animals underwent training for the inhibitoryavoidance task and were tested 24 h later. The aerobic exercise attenuated the long-term memory deﬁcit induced by 96 h of paradoxical SD. Western blot analysis of the hippocampus revealed increased levels of GAP-43 in exercised rats. However, the expression of synapsin I, synaptophysin, and PSD-95 was not modiﬁed by either exercise or SD. Our results suggest that an aerobic exercise program can attenuate the deleterious effects of SD on long-term memory and that this effect is not directly related to changes in the expression of the pre- and post-synaptic proteins analyzed in the study.
A single ECS administered immediately after training produces retrograde amnesia in rodents (3). Anterograde deficits have been reported when ECS is administered 1 h before training in inhibitoryavoidance, but not after an interval of 24 h (4-7). The objec- tive of the present study was to investigate the effect of a single ECS administered at different time intervals before the simulta- neous training in inhibitoryavoidance and cued fear classical conditioning, tasks that were shown to be selectively affected by the repeated ECS regimen (2).
Blandina et al. (12) have suggested that the facilitatory or inhibitory effects of histamine on learning and memory processes are related, among other factors, to the brain structure involved and to the nature of the task performed. Thus, the purpose of the present study was to determine the pharmacological effect of post-training administration of the histaminergic precursor L-histidine (LH) on the mem- ory consolidation of inhibitoryavoidance by Carassius auratus submitted to cerebellar ablation.
through their antagonism of cation-chloride cotransporters. Given that loop diuretics may act as antiepileptic drugs that modulate GABAergic signaling, we sought to investigate whether they also affect hippocampal function. The current study was performed to evaluate the possible role of NKCC1 on the hippocampal function. Brain slice extracellular recording, inhibitoryavoidance, and western blot were applied in this study. Results showed that hippocampal Long-term potentiation was attenuated by suprafusion of NKCC1 inhibitor bumetanide, in a dose dependent manner. Sequent experiment result showed that Intravenous injection of bumetanide (15.2 mg/kg) 30 min prior to the training session blocked inhibitoryavoidance learning significantly. Subsequent control experiment’s results excluded the possible non-specific effect of bumetanide on avoidance learning. We also found the phosphorylation of hippocampal MAPK was attenuated after bumetanide administration. These results suggested that hippocampal NKCC1 may via MAPK signaling cascade to possess its function.
The results of the present study suggest that CPA improves memory of the inhibitoryavoidance task in telen- cephalic-ablated fish. Albeit, there were no differences between groups at the beginning and the end of the experi- mental procedure, CPA-8 group retained performance on the 3rd day. Cofiel and Mattioli (7) found similar results in a study performed on intact goldfish with the same experi- mental model in which the group treated with 8 mg/kg CPA presented a significant increase in latency before leaving the start compartment. The present study confirms and extends the action of CPA on conditioning of inhibitoryavoidance by suggesting that these effects occur via mes- encephalic and/or diencephalic structures, as the action of CPA was the same in animals submitted or not to telence- phalic ablation.
The present article tested the influence of estrous cycle phase on the anxiolytic and panicolytic-like effects of diazepam, using the elevated T-maze, a rodent anxiety model. The results indicate a modulatory action of gender and hormonal status on the effects of diazepam in the elevated T-maze, evident in anxiety- like (inhibitoryavoidance) but not fear-like behaviors (escape), in the diestrus and proestrus phases, correspondent to an increase in the circulating levels of estrogen present in female rats’ organisms. These results are consistent with available evidence regarding increased anxiety and estrogen levels (Bitran & Dowd, 1995; Díaz-Véliz, Alarcón, Espinoza, Dussabaut, & Mora, 1997; Díaz-Véliz, Soto, Dussabaut, & Mora, 1989; Gouveia et al., 2004; Gouveia & Morato, 2002). Females in diestrus and proestrus also presented reduced latency times in inhibitoryavoidance trials in relation to males and females in metaestrus and diestrus, suggesting an anxiolytic effect of progesterone also consistent with the literature (Frye et al., 2000; Frye & Walf, 2002; Frye, Walf, Rhodes, & Harney, 2004; Guilinello et al., 2001; Rhodes & Frye, 2001; Smith et al., 1998). The significant increases in latency times on males’ inhibitoryavoidance trials are proportional to the dose of diazepam, suggesting not a neuromodulatory phenomenon, but a sedative and ataxic effect of this benzodiazepine.
There were no differences among groups in the inhibitoryavoidance training session. In the test session, there were significant differences (P<0.05) between diazepam- injected animals (1 mg/kg) and animals that received propericiazine (0.05, 0.075 and 0.01 mg/kg). Animals treated with diazepam did not show differences in the training or test latencies, demonstrating the amnestic effect of this drug. The group treated with properi- ciazine at doses of 0.05, 0.075 and 0.1 mg/ kg, on the other hand, showed a significant increase in the latency to step down in the test session when compared with the training session (P<0.05), indicating that memory was acquired for this task. The same behav- ior was observed for the saline (P<0.05) and vehicle groups (P<0.05). These results show
The British psychologist Sheila Handley, who con- ceived the idea of the crossed elevated maze, has argued that many of the inconsistencies found with drugs that alter 5-HT neurotransmission in the elevated X and plus mazes may be explained by the fact that these are mixed models, in the sense that the rat displays different strate- gies of defense while exploring them, which could be influenced in opposite directions by 5-HT (Handley et al. 1993). At least two strategies may be easily seen: 1) avoidance of open arms when the rat is in one of the closed arms, and 2) escape from an open arm to enter a safer, closed arm. This observation led to the idea of separating these behavioral tasks: inhibitoryavoidance and one-way escape, a goal that has been achieved by building the elevated T-maze (Graeff et al. 1993).
constrictor snakes can be considered as a more etho- logically acceptable alternative to study the defensive repertoires of different species of rodents confronted with venomous and Boidae snakes. This approach can be useful to investigate feeding preferences considering the different sizes of laboratory animals. Despite the high frequency of interaction between gerbils and Boidae snakes, no feeding preference was observed when the constrictor snakes Boa constrictor amarali and Figure 2 Instinctive fear-induced defensive responses evoked by Mus musculus confronted with the South American Viperidae snakes Crotalus durissus terrificus (A, B, C) and Bothrops alternatus (D and E) for 5 min in a polygonal arena with a burrow. Anxiety/fear-related response: alertness (A) elicited in the presence of the rattlesnake, and inhibitoryavoidance (E, e’) displayed in the presence of Bothrops alternatus. Panic attack-like responses: freezing (B) displayed by prey threatened by a rattlesnake, and non- oriented escape (D) displayed by prey threatened by Bothrops alternatus venomous snake.
We examined the expression of genes related to brain energy metabolism and particularly those encoding glia (astrocyte)-specific functions in the dorsal hippocampus subsequent to learning. Context-dependent avoidance behavior was tested in mice using the step-through InhibitoryAvoidance (IA) paradigm. Animals were sacrificed 3, 9, 24, or 72 hours after train- ing or 3 hours after retention testing. The quantitative determination of mRNA levels revealed learning-induced changes in the expression of genes thought to be involved in astrocyte-neuron metabolic coupling in a time dependent manner. Twenty four hours follow- ing IA training, an enhanced gene expression was seen, particularly for genes encoding monocarboxylate transporters 1 and 4 (MCT1, MCT4), alpha2 subunit of the Na/K-ATPase and glucose transporter type 1. To assess the functional role for one of these genes in learn- ing, we studied MCT1 deficient mice and found that they exhibit impaired memory in the inhibitoryavoidance task. Together, these observations indicate that neuron-glia metabolic coupling undergoes metabolic adaptations following learning as indicated by the change in expression of key metabolic genes.
Animals were selected randomly, and four groups were used: male sham-exposed (n = 10), male exposed to 8 mT (n = 10), female sham-exposed (n = 10), female exposed to 8 mT (n = 10). Before each learning session, the animals that were selected for the experimental groups were exposed to an 8 mT, 50 Hz EMF in the coil. After 60 minutes exposure, they were subjected to the avoidance learning task in the learning session. The animals in the sham-exposed control groups were placed in the coil for 60 min. without an EMF. Twenty-four hours after the test session, each animal was placed on the platform of the inhibitoryavoidance apparatus, and the step-down latency for each animal was measured and recorded as an index of passive avoidance learning.
study we have demonstrated that the alkaloids present in the hydroalcoholic extract of E. mulungu are responsible, at least in part, for its anxiolytic effects recorded in the ETM. Briefly, acute p.o. treatment with erythravine (3, 10 mg/kg), (⫹)- 11 a-hydroxy-erythravine (3, 10 mg/kg) and (⫹)-a-hydroxy- erysotrine (3, 10 mg/kg) impaired the inhibitoryavoidance acquisition from the open arms of the ETM for mice, sug- gesting an anxiolytic effect of these erythrinian compounds. 4)
In the elevated T-maze, inhibitory avoid- ance and escape responses are measured in a maze consisting of three elevated arms - one of them enclosed and two open. For inhibi- tory avoidance measurement, rats are placed at the distal end of the enclosed arm and the latency to withdraw from this arm with the four paws is recorded in three successive trials. Because of their innate fear of height and openness (10), rats learn to remain longer in the enclosed arm over trials, indicating the acquisition of inhibitoryavoidance to the open arms. On the other hand, when the animals are placed at the end of one of the open arms they move towards the enclosed arm, presumably performing an escape re- sponse. Based on the effects of different classes of anxiety-modulating drugs in this test, inhibitoryavoidance has been related to generalized anxiety disorder (GAD) and es-
64. Quevedo J, Moretto A, Colvero M, Roesler R, Ferreira MB. The N- methyl-D-aspartate receptor blocker MK-801 prevents the facilitatory effects of naloxone and epinephrine on retention of inhibitoryavoidance task in rats. Behav Pharmacol 1997;8:471-4. 65. Quevedo J, Vianna M, Zanatta MS, Roesler R, Izquierdo I, Jerusalinsky D, Quillfeldt JA. Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory. Behav Pharmacol 1997;8:713-7.