Intra-nucleus accumbens shell injection of baclofen blocks the reconsolidation of conditioned place preference in morphine-addicted mice / 生理学报

Preclinical studies suggest that the GABA receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABA receptor agonist, is the only specific GABA receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABA receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 μL/side or 0.12 nmol/0.2 μL/side), rather than vehicle or BLF (0.01 nmol/0.2 μL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABA receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.

The electrophysiological response of chorda tympani nerve to taste stimuli in rats with conditioned taste aversion to saltiness / 中国应用生理学杂志

OBJECTIVE@#To explore the characteristic changes of the peripheral chorda tympanic nerve (CT) electrophysiological responses to salty stimulus and other taste stimuli in rats with the conditioned taste aversion to saltiness.@*METHODS@#Fourteen adult SD male rats were divided into a conditioned taste aversion to salty group (CTA) and a control group (Ctrl) (n=7/group). On the first day of the experiment, rats were given a 0.1 mol/L NaCl intake for 30 min, then, the rats in CTA and Ctrl groups were injected intraperitoneally with 2 ml of 0.15 mol/L LiCl and the same amount of saline respectively. On day 2, 3 and 4, the 30 min consumption of NaCl and distilled water was measured for both groups of rats. On the 4th day after the behavioral test of that day, CT electrophysiological recording experiments were performed on CTA rats and control rats.@*RESULTS@#Compared with the rats in Ctrl group, the electrophysiological characteristics of CT in CTA group rats did not change significantly the responses to the series of NaCl and other four basic taste stimuli (P＞0.05). The amiloride, the epithelial sodium channel blocker, strongly inhibited the response of CT to NaCl in CTA and Ctrl group rats (P＜0.01).@*CONCLUSION@#The electrophysiological responses of CT to various gustatory stimuli do not significantly change in rats after the establishment of conditional taste aversion to the saltiness.

Relationship between level of readiness for self-directed learning and learning styles of CEU nursing students

This study aimed to assess the level of readiness of student nurses for self-directed learning and their learning styles. It also determined the relationship between the two factors and the relationship of each factor to the respondents' demographic profile. This descriptive- correlational study utilized the Autonomous Learner Index of Abu- Moghli, Khalaf, Halabi & Wardam (2005) to assess the students' level of readiness in self-directed learning, and the Learning Style Inventory of Kolb & Kolb (2005) to assess their learning style type. No sampling technique was used because total population was included covering all 103 regular nursing students of Centro Escolar University for First semester of academic year 2016-2017. The study underwent Ethics Review Board Approval before it was implemented. Results of the study revealed that most of the nursing students were independent learners (52%). There were no dependent learners but since there were several respondents who were uncertain (48%), it is the role of nurse educators to develop their independence in learning. Moreover, all the four types of learning styles namely: Accommodative, Convergent, Assimilative and Divergent; were present showing the variation in learning styles of nursing students. But it was found out that they mostly prefer the Convergent learning style, especially the junior and senior students. The study concluded that there was no relationship between the variables: demographic profile, self-directed learning readiness and learning style. However, the scores of convergent learning style were higher than that of divergent and accommodative in their self-directed learning readiness.

Relationship between level of readiness for self-directed learning and learning styles of CEU nursing students

This study aimed to assess the level of readiness of student nurses for self-directed learning and their learning styles. It also determined the relationship between the two factors and the relationship of each factor to the respondents' demographic profile. This descriptive- correlational study utilized the Autonomous Learner Index of Abu- Moghli, Khalaf, Halabi & Wardam (2005) to assess the students' level of readiness in self-directed learning, and the Learning Style Inventory of Kolb & Kolb (2005) to assess their learning style type. No sampling technique was used because total population was included covering all 103 regular nursing students of Centro Escolar University for First semester of academic year 2016-2017. The study underwent Ethics Review Board Approval before it was implemented. Results of the study revealed that most of the nursing students were independent learners (52%). There were no dependent learners but since there were several respondents who were uncertain (48%), it is the role of nurse educators to develop their independence in learning. Moreover, all the four types of learning styles namely: Accommodative, Convergent, Assimilative and Divergent; were present showing the variation in learning styles of nursing students. But it was found out that they mostly prefer the Convergent learning style, especially the junior and senior students. The study concluded that there was no relationship between the variables: demographic profile, self-directed learning readiness and learning style. However, the scores of convergent learning style were higher than that of divergent and accommodative in their self-directed learning readiness.

Optogenetic activation of dorsal hippocampal astrocytic Rac1 blocks the learning of associative memory / 生理学报

Rac1 belongs to the family of Rho GTPases, and plays important roles in the brain function. It affects the cell migration and axon guidance via regulating the cytoskeleton and cellular morphology. However, the effect of its dynamic activation in regulating physiological function remains unclear. Recently, a photoactivatable analogue of Rac1 (PA-Rac1) has been developed, allowing the activation of Rac1 by the specific wavelength of light in living cells. Thus, we constructed recombinant adeno-associated virus (AAV) of PA-Rac1 and its light-insensitive mutant PA-Rac1-C450A under the control of the mouse glial fibrillary acidic protein (mGFAP) promoter to manipulate Rac1 activity in astrocytes by optical stimulation. Primary culture of hippocampal astrocytes was infected with the recombinant AAV-PA-Rac1 or AAV-PA-Rac1-C450A. Real-time fluorescence imaging showed that the cell membrane of the astrocyte expressing PA-Rac1 protruded near the light spot, while the astrocyte expressing PA-Rac1-C450A did not. We injected AAV-PA-Rac1 and AAV-PA-Rac1-C450A into dorsal hippocampus to investigate the role of the activation of Rac1 in regulating the associative learning. With optical stimulation, the PA-Rac1 group, rather than the PA-Rac1-C450A group, showed slower learning curve during the fear conditioning compared with the control group, indicating that activating astrocytic Rac1 blocks the formation of contextual memory. Our data suggest that the activation of Rac1 in dorsal hippocampal astrocyte plays an important role in the associative learning.

Sucrose reward promotes rats' motivation for cocaine / 生理学报

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

The influence of sex and menstrual cycle on conditioned acquisition and extinction: Event-related potential research / 生理学报

Previous studies have indicated phase-related differences in conditioned acquisition and extinction. In recent years, many researchers used event-related potential (ERP) technology to assess the extent of the acquisition and extinction. Therefore, this study was aimed to assess the sex- and menstrual cycle-dependent effects on the conditioned acquisition and extinction using ERP technology. Thirty-two females at two phases (menses phase, FM, and luteal phase, FL) of their menstrual cycle and 16 males participated in the experiment. The experiment consisted of two stages: acquisition stage and extinction stage. In the acquisition stage, in the predictable context, a condition stimulus (CS) was always followed by the presentation of a negative picture or a neutral picture; but in the unpredictable context, a CS was paired with a negative picture or a neutral picture 20% of the time. In the extinction stage, only CS was presented. The results showed that at acquisition stage, significant larger P2 amplitudes were recorded in female subjects in FL and FM in comparison with those of males. The female subjects in FL may acquire the strongest CS-US conditional connection. At extinction stage, the female subjects in FL showed larger P2 amplitudes than males, but there were no significant differences in P2 amplitudes between the males and females in FM. The results suggest that the females in FL allocate more attention resources to the acquisition of a conditioned response and delayed extinction. In conclusion, we suggest that female menstrual cycle may modulate conditioned acquisition and extinction processes, and our ERP data may provide an explanation for the premenstrual dysphoric disorder.

Subchronic effects of fluoxetine on conditioned suppression produced by a hot air blast

Conditioned suppression is an animal model of anxiety disorders that has been broadly used to investigate the behavioral effects of different drugs. However, various methodological variables (e.g., the type of aversive stimulus) that supposedly interfere with the acquisition of conditioned suppression may also contribute to conflicting results among the studied drugs. Additionally, few studies have sought to investigate the effects of selective serotonin reuptake inhibitors (SSRIs). The present study investigated the effect of subchronic 5-day administration of 5 mg/kg fluoxetine in the retention of conditioned suppression produced by a hot air blast (HAB). The subjects were 12 albino Wistar rats distributed into an Experimental Group (EG) and Control Group (CG). After sessions were conducted to pair two stimuli, a sound and HAB, fluoxetine (EG) or saline (CG) was administered. Twenty-four hours after the last injection, a test session was conducted. The results showed no difference between groups. Fluoxetine (5 mg/kg) did not exert anxiolytic effects in this model of conditioned suppression produced by a HAB.

Reinstatement of short-latency responses after asymptotic Pavlovian conditioning training by the presentation of an extraneous stimulus

The purpose of this study was to examine whether the progressive disappearance of short-latency conditioned responses, or inhibition of delay, observed in Pavlovian conditioning with long inter-stimulus intervals, could be reverted by the presentation of a novel stimulus. In one experiment, two groups of rabbits received extensive training with a short (250 ms) or a long (1500 ms) tone that overlapped and terminated with a periorbital shock unconditioned stimulus. After training, the presentation of an extraneous stimulus prior to tone onset produced a reinstatement of short latency CRs in the group trained with the long CS, but did not affect CR latency in the group trained with the short CS. This finding is consistent with Pavlov's (1927) view that conditioning with long conditioned stimuli involves the acquisition of response tendencies in the early portion of the stimulus that are subsequently suppressed by the development of an inhibitory process.

Modulación contextual en la extinción: recuperación de una aversión condicionada al sabor en un tercer contexto / Modulação contextual na extinção: recuperação de uma aversão condicionada ao sabor em um terceiro contexto / Contextual modulation of extinction: recovery of taste-aversion conditioning in a third context

Este experimento se diseñó para evaluar la renovación ABC con un procedimiento de condicionamiento de aversión al sabor (CAS) en tres fases: adquisición, extinción y prueba. Durante la adquisición, 15 ratas Wistar, asignadas a los grupos ABC y ABB, tuvieron acceso a una solución con sacarosa y posteriormente recibieron una inyección de cloruro de litio (liCl) en el Contexto A. En la extinción, ambos grupos bebieron la solución con sacarosa sin la administración del liCl en el Contexto B. En la prueba, los grupos tuvieron acceso a la solución con sacarosa sin administrarles liCl en el contexto de extinción para el grupo ABB, y en un tercer contexto para el grupo ABC. Los resultados mostraron la recuperación de la aversión condicionada al sabor únicamente en el grupo ABC.

This experiment was designed to evaluate ABC renewal in a conditioned taste aversion (CTA) procedure consisting of three phases: acquisition, extinction and test. During the acquisition phase, 15 Wistar rats assigned to groups ABC and ABB had access to a sucrose solution, after which they were injected with lithium chloride (liCl) in Context A. In the extinction phase, both groups of rats had access to the sucrose solution in Context B, but no liCl was administered. Finally, during the test, group ABB received sucrose solution without liCl in the extinction context, while group ABC was tested in a third context. Results showed renewal of conditioned taste aversion only in the ABC group.

Este experimento foi elaborado para avaliar a renovação ABC com um procedimento de condicionamento de aversão ao sabor (CAS) em três fases: aquisição, extinção e prova. Durante a aquisição, 15 ratos Wistar, designados aos grupos ABC e ABB, tiveram acesso a uma solução com sacarose e posteriormente receberam uma injeção de cloreto de lítio (liCl) em Contexto a. Na extinção, ambos grupos beberam a solução com sacarose sem a administração do liCl em Contexto B. Na prova, os grupos tiveram acesso à solução com sacarose sem administrar-lhes liCl num contexto de extinção para o grupo ABB, e num terceiro contexto para o grupo ABC. Os resultados mostraram a recuperação da aversão condicionada ao sabor unicamente no grupo ABC.

Induction of Zenk protein expression within the nucleus taeniae of the amygdala of pigeons following tone and shock stimulation

In this study, we evaluated the expression of the Zenk protein within the nucleus taeniae of the pigeon’s amygdala (TnA) after training in a classical aversive conditioning, in order to improve our understanding of its functional role in birds. Thirty-two 18-month-old adult male pigeons (Columba livia), weighing on average 350 g, were trained under different conditions: with tone-shock associations (experimental group; EG); with shock-alone presentations (shock group; SG); with tone-alone presentations (tone group; TG); with exposure to the training chamber without stimulation (context group; CG), and with daily handling (naive group; NG). The number of immunoreactive nuclei was counted in the whole TnA region and is reported as density of Zenk-positive nuclei. This density of Zenk-positive cells in the TnA was significantly greater for the EG, SG and TG than for the CG and NG (P < 0.05). The data indicate an expression of Zenk in the TnA that was driven by experience, supporting the role of this brain area as a critical element for neural processing of aversive stimuli as well as meaningful novel stimuli.

Dinâmica do sistema córtico-hipocampal durante o condicionamento contextual de medo / Cortico-hippocampal system dynamics during contextual fear conditioning

O estabelecimento das memórias de longo prazo requer uma efetiva comunicação do hipocampo com o neocortex. Um mecanismo plausível envolvido na comunicação neuronal e na plasticidade sináptica é a sincronização da atividade elétrica cerebral na frequência teta. Estudos recentes mostraram que a sincronização entre os ritmos teta do hipocampo e do córtex pré-frontal aumenta durante a evocação das memórias aversivas e diminui após a extinção do aprendizado. Entretanto, outros ritmos cerebrais, como as ondas delta, também estão envolvidos nas respostas comportamentais do medo e nos processos de memória. Desta forma, o ritmo teta, que já foi bastante estudado pelo seu papel no aprendizado e na memória, e o ritmo delta, por seu envolvimento no ciclo sono-vigília, foram investigados considerando a relação causal entre eles. Ainda não está bem estabelecido como os ritmos delta e teta podem juntos contribuir nos processos cognitivos ou como os ritmos do hipocampo podem influenciar ou receber influencias da atividade cortical. Neste trabalho foi investigada a contribuição dos ritmos delta e teta em função do estado comportamental (vigília ativa ou congelamento) e do tipo de memória evocada (recente ou remota). Além disso, foi realizada uma análise de sincronia de fase para inferir a dinâmica da atividade elétrica entre o córtex pré-frontal medial, o hipocampo e o córtex visual durante a evocação das memórias de medo. Para tanto, os animais foram treinados e testados numa tarefa de condicionamento de medo ao contexto. Neste tipo de condicionamento, o animal aprende a estabelecer uma associação entre um determinado contexto (caixa de condicionamento) e um evento aversivo (choque elétrico nas patas) que ocorreu neste contexto...

The establishment of long-term memories requires effective communication of the hippocampus to the neocortex. Electrophysiological activities between hippocampus and prefrontal cortex have shown higher theta synchronization during retrieval of aversive memories and lower during extinction learning. While theta activity is more differently related to learning and memory, delta waves have been more discussed in the context of sleep or "offline" states. Few studies have investigated delta waves during "on-line" states (such as task-relevant situations) and the contribution of these rhythms to memory storage remains unclear. We recorded electrophysiological data to study the contributions of delta and theta waves in cortico-hippocampal system of rats underwent to contextual fear conditioning. Our experiment consisted of environmental pre-exposition, training with electrical footshocks, and recent/remote memory tests. Two groups of rats were tested one or eighteen days post training for recent or remote memory, respectively. Local field potential time series of two behavioral states were sampled: active exploration and freezing. The results showed that theta and delta rhythms play an important role in behavioral responses and memory processing. They are related to fear recall and their contribution depend on the recent or remote memory. Additionally, using an order parameter we show that theta contribution is strongly pronounced in active exploration, decreasing during freezing. In the latter, the rats presented pronounced delta waves in freezing. Moreover, a behavioral-dependent causality measure showed an increase of theta influence in delta rhythms, resulting in a theta slowing in aversive memory retrieval. Finally, we show an increased synchrony between hippocampus and prefrontal cortex during recall of recent memory, but a decreased synchrony in remote memory...

Chronic nicotine enhances contextual fear memory in rats / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of chronic nicotine on contextual fear memory in rats.@*METHODS@#Rats were subcutaneously injected saline or nicotine for 14 days continuously to induce nicotine dependence. Somatic signs of spontaneous nicotine withdrawal were assessed on day 1 and 14 after the last injection. Locomotor activity was tested 13 days after the last injection. Contextual fear conditioning task was run 14 days after the last injection, which included 3 phases: habituation, fear conditioning, and test. Percent freezing was used as an index for fear memory during the conditioning and test phases. Finally, footshock sensitivity test was conducted.@*RESULTS@#Compared with the saline group, the global withdrawal scores significantly increased in the nicotine group when the somatic signs were assessed 1 day after the nicotine injection, while there was almost no difference in the 2 groups 14 days after the last injection. In the contextual task, the nicotine group showed a significant increase in the level of freezing response during the test phase but not in the conditioning phase. There was no significant difference in the locomotor activity and footshock sensitivity between the 2 groups.@*CONCLUSION@#Chronic nicotine enhances the contextual fear memory in rats. This effect is not attributed to the change of somatic signs, locomotor activity or footshock sensitivity.

Learning processes and the neural analysis of conditioning

Classical and operant conditioning principles, such as the behavioral discrepancy-derived assumption that reinforcement always selects antecedent stimulus and response relations, have been studied at the neural level, mainly by observing the strengthening of neuronal responses or synaptic connections. A review of the literature on the neural basis of behavior provided extensive scientific data that indicate a synthesis between the two conditioning processes based mainly on stimulus control in learning tasks. The resulting analysis revealed the following aspects. Dopamine acts as a behavioral discrepancy signal in the midbrain pathway of positive reinforcement, leading toward the nucleus accumbens. Dopamine modulates both types of conditioning in the Aplysia mollusk and in mammals. In vivo and in vitro mollusk preparations show convergence of both types of conditioning in the same motor neuron. Frontal cortical neurons are involved in behavioral discrimination in reversal and extinction procedures, and these neurons preferentially deliver glutamate through conditioned stimulus or discriminative stimulus pathways. Discriminative neural responses can reliably precede operant movements and can also be common to stimuli that share complex symbolic relations. The present article discusses convergent and divergent points between conditioning paradigms at the neural level of analysis to advance our knowledge on reinforcement

Prior exposure to stress delays extinction but does not modify reinstatement of nicotine-induced conditioned place preference

Studies in humans suggest that exposure to stress is related to relapse to tobacco use. The reinstatement of conditioned place preference (CPP) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. The present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced CPP. Adult male Wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. One day after the last stress session the CPP protocol was carried out. Nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). Once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). The animals that did not show extinction of CPP were submitted to two other extinction sessions. Following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. Both control and stress groups showed reinstatement of CPP. The percentage of rats from the stress group that extinguished nicotine-CPP in the first and second test was lower as compared to the control group. In conclusion, stress delayed the extinction of the nicotine-induced CPP, but did not modify the reinstatement.

Sound level of conditioned stimulus differs the plasticity of characteristic frequency in the rat cortical neurons / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Try to observe the plasticity of neuron in primary cortex of rat evoked by conditioned stimulus of different sound level.</p><p><b>METHODS</b>Applying conventional electrophysiological technique of extracellular recording to investigate the plasticity of characteristic frequency (CF) and frequency turning curve (FIC) of neurons in rat auditory cortex (AC) by determining CF shifts of neurons caused by sound stimulus of different sound level.</p><p><b>RESULTS</b>When the frequency difference between conditioned stimulus (CS) frequency and the CF of neuron was in 1.0 kHz, the plasticity of CF induced by CS was associated with sound level. The probability of the plasticity of CF evoked by CS of higher sound lever was more than the lower. And the probability was dependent on frequency turning curve (FTC) and almost independent on the sound level of conditioned signal.</p><p><b>CONCLUSION</b>Sound level of conditioned stimulus differs the plasticity of characteristic frequency of neurons in rat auditory cortex.</p>

Strain and sex differences in fear conditioning: 22 kHz ultrasonic vocalizations and freezing in rats

Strain and sex differences in fear conditioning were investigated in two commonly used laboratory rats: Sprague Dawleys and Long-Evans. Twenty-two kHz ultrasonic vocalization (USV) distress calls and freezing behavior were used to measure fear responses to contextual and auditory conditioned stimuli (CSs), which were previously paired with a footshock unconditioned stimulus (US). Both strain and sex had significant effects on USVs and freezing during training and subsequent context and tone tests. Overall, the male Sprague Dawley rats froze and emitted USVs more than the other groups. Additionally, levels of freezing and USVs were differentially influenced by the type of CS (context or tone). These results suggest that species-specific defense responses in laboratory rats are highly influenced by the strain and sex of the subject, and that these factors should be considered in future fear conditioning studies.

A emergência de relações condicionais entre estímulos como resultado de treino de série de discriminações simples simultâneas / The emergence of conditional relationships among stimuli resulting from serial training of simple, simultaneous discriminations

O procedimento de emparelhamento de acordo com o modelo tem sido privilegiado para o estabelecimento de discriminações condicionais entre estímulos e para testar a emergência de classes de estímulos equivalentes. No entanto, outros procedimentos de treino discriminativo também têm sido efetivos para o estabelecimento destas classes. Este trabalho teve por objetivo estudar um procedimento de discriminação simples que, com base em discriminações simples já existentes, promoveria a emergência de relações condicionais entre estímulos. Participaram do estudo seis crianças (de seis e sete anos de idade) que trabalharam em computador. Depois de estabelecida uma discriminação simples entre dois estímulos, estes foram sobrepostos a novos estímulos, até a formação de nova discriminação. O mesmo procedimento foi repetido com outros estímulos. Depois de treino discriminativo no qual um participante apresentou apenas seis erros e os demais apresentaram três ou menos erros, testou-se a emergência de relações entre estímulos. Os testes revelaram que houve formação de classes de estímulos equivalentes para três participantes e sugeriram esta possibilidade para outros dois.

A number of studies have shown the possibility of using series of simple discriminations and multiple reversals to establish equivalent stimulus classes. The current study aimed to test the possibility of establishing equivalence classes through a training procedure that established simple discriminations on the basis of previously established ones, without reversals. Participants consisted of 6 children, aged 6 and 7. After the initial discrimination training of a pair of stimuli, two new, simple discriminations were established, one at a time, using the superimposition of stimuli. Following training, conditional relations between stimuli were tested. Results showed that all participants learned the discriminations almost without error: one participant had 6 errors and all the others had three errors or fewer. Tests for the emergence of classes of equivalent stimuli were positive for 3 participants and suggested the possibility of such emergence for 2 other participants.

Chlorpheniramine facilitates inhibitory avoidance in teleosts submitted to telencephalic ablation

The present study investigated the involvement of H(1) histaminegic receptor on the acquisition of inhibitory avoidance in Carassius auratus submitted to telencephalic ablation. The fish were submitted to telencephalic ablation 5 days before the experiment. The inhibitory avoidance procedure included 1 day for habituation, 3 days for training composed of 3 trials each (1st day: T1, T2, T3; 2nd day: 2T1, 2T2, 2T3; 3rd day: 3T1, 3T2, 3T3) and 1 day for test. On training days, the fish were placed in a white compartment, after 30 s the door was opened. When the fish crossed to a black compartment, a weight was dropped (aversive stimuli). Immediately after the third trial, on training days, the fish received, intraperitoneally, one of the pharmacological treatments (saline (N = 20), 8 (N = 12) or 16 (N = 13) µg/g chlorpheniramine, CPA). On the test day, the time to cross to the black compartment was determined. The latency of the saline group increased significantly only on the 3rd trial of the 2nd training day (mean ± SEM, T1 (50.40 ± 11.69), 2T3 (226.05 ± 25.01); ANOVA: P = 0.0249, Dunn test: P < 0.05). The group that received 8 µg/g CPA showed increased latencies from the 2nd training day until the test day (T1 (53.08 ± 17.17), 2T2 (197.75 ± 35.02), test (220.08 ± 30.98); ANOVA: P = 0.0022, Dunn test: P < 0.05)). These results indicate that CPA had a facilitating effect on memory. We suggest that the fish submitted to telencephalic ablation were able to learn due to the local circuits of the mesencephalon and/or diencephalon and that CPA interferes in these circuits, probably due an anxiolytic-like effect.

The time course of ethanol tolerance: associative learning

The effect of different contextual stimuli on different ethanol-induced internal states was investigated during the time course of both the hypothermic effect of the drug and of drug tolerance. Minimitters were surgically implanted in 16 Wistar rats to assess changes in their body temperature under the effect of ethanol. Rat groups were submitted to ethanol or saline trials every other day. The animals were divided into two groups, one receiving a constant dose (CD) of ethanol injected intraperitoneally, and the other receiving increasing doses (ID) during the 10 training sessions. During the ethanol training sessions, conditioned stimuli A (tone) and B (buzzer) were presented at "state +" (35 min after drug injection) and "state -" (170 min after drug injection), respectively. Conditioned stimuli C (bip) and D (white noise) were presented at moments equivalent to stimuli A and B, respectively, but during the saline training sessions. All stimuli lasted 15 min. The CD group, but not the ID group, developed tolerance to the hypothermic effect of ethanol. Stimulus A (associated with drug "state +") induced hyperthermia with saline injection in the ID group. Stimulus B (associated with drug "state -") reduced ethanol tolerance in the CD group and modulated the hypothermic effect of the drug in the ID group. These results indicate that contextual stimuli acquire modulatory conditioned properties that are associated with the time course of both the action of the drug and the development of drug tolerance.