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Recent research has suggested that among different relapse procedures (i.e. resurgence and renewal), an increased number of acquisition sessions contributes on observing a greater relapse. Even when such results seem to be consistent across studies, these can also be explained by attending to the number of scheduled reinforcers, since using different number of acquisition sessions could also result on differences in the number of scheduled reinforcers between groups. ABA renewal was assessed in four groups of rats by varying the number of acquisition sessions (12 and 4) or the number of scheduled reinforcers (240 and 720) between groups. As previous experiments, our results suggest that different number of acquisition sessions results on differences in ABA renewal; nevertheless, different number of obtained reinforcers seem to affect the degree to which renewal is observed. Therefore, it seems like renewal does not only depend upon the amount of training but also on the number of reinforcers obtained during acquisition. [ABSTRACT FROM AUTHOR]

Abstract: Post-extinction exposure of rats to a sub-conditioning procedure can evoke conditioned fear, which may correspond to fear return and/or fear learning potentiation. The aim of the present study was to clarify this issue and examine the effects of tetanic stimulation of the hippocampus (HPC) and medial prefrontal cortex (mPFC), two brain regions implicated in post-extinction modulation of conditioned fear. Rats were initially submitted to five tone-shock pairings with either a 0.7-mA or 0.1-mA shock. Tone-evoked freezing was observed only with the higher shock intensity, indicating that the 0.1-mA shock corresponded to a sub-conditioning procedure. All conditioned rats underwent fear extinction with 20 tone-alone trials. When retrained with the sub-conditioning procedure, they displayed again tone-evoked freezing, except when the initial tone was unpaired or a new tone was paired with the 0.1-mA shock, demonstrating fear return rather than fear learning potentiation. We also found that HPC and mPFC tetanic stimulations, applied 24h after the sub-conditioning procedure, similarly reduced this fear return. However, mPFC inactivation abolished temporary HPC tetanus effect, whereas HPC inactivation did not interfere with mPFC tetanus effect. These data confirm our previous findings and reveal the nature of HPC-mPFC interactions in post-extinction modulation of conditioned fear. [Copyright &y& Elsevier]

Abstract: Three experiments with rat subjects examined resurgence of an extinguished instrumental response using the procedure introduced by with pigeons. There were three phases: (1) initial acquisition of pressing on a lever (L1) for pellet reward, (2) extinction of L1, and (3) a test session in which a second lever (L2) was inserted, briefly reinforced, and then extinguished. Experiment 1 confirmed that if pressing L2 delivered 20 pellets followed by extinction, rats would resume L1 responding in the final test. Experiment 2 compared the effects of response-contingent and non-contingent rewards delivered upon insertion of L2. Although insertion of L2 alone did not increase L1 responding, response-contingent and non-contingent rewards led to comparable increases in L1 responding. Experiment 3 found that the delivery of non-contingent pellets during extinction of L1, which would be expected to reduce the ability of pellets to set the occasion for the L1 response, also reduced the effects of both response-contingent and non-contingent rewards during the final test. The results indicate that in this method, the resurgence treatment leads to an increase in L1 pressing due to simple presentation of the pellet; delivering the reinforcer after extinction of L1 reinstates L1 responding by setting the occasion for the L1 response. [Copyright &y& Elsevier]

Abstract: In this study, we investigated how midazolam and d-cycloserine regulate the tonic activity and/or phasic reactivity of brain neurotransmitter systems to fear-evoking stimuli in rats with varying intensities of a fear response. We used a new animal model composed of high (HR) and low (LR) anxiety rats, selected according to their behaviour in the contextual fear test (i.e., the duration of a freezing response was used as a discriminating variable). In these rats, we examined the effects of both drugs on the release of glutamate and GABA in the basolateral amygdala (BLA) during the first extinction trial of a conditioned fear test. The results showed that administration of d-cycloserine (15mg/kg, i.p.) significantly enhanced the inhibition of an aversive context-induced freezing response observed during the extinction session in HR and LR rats. In contrast, midazolam (0.75mg/kg, i.p.) accelerated the attenuation of fear responses only in HR rats. The less anxious behaviour of LR animals given saline was accompanied by elevated basal levels of glutamate in the BLA, in comparison with HR rats, and a stronger elevation of GABA in response to contextual fear. In HR animals, the pretreatment of rats with d-cycloserine and midazolam significantly increased the local concentration of GABA and inhibited the expression of contextual fear. These findings suggest that animals more vulnerable to stress have innate deficits in brain systems that control the activity of the BLA mediating the central effect of stress. These results contribute to our understanding of observed individual differences in the effects of anxiolytic drugs among patients with anxiety disorders. [Copyright &y& Elsevier]

Abstract: Chronic stress produces dendritic retraction in medial prefrontal cortex and impairs retrieval of extinction of conditioned fear, a behavior mediated by the infralimbic region (IL) of medial prefrontal cortex. To test the hypothesis that stress-induced changes in IL contribute to the stress-induced impairment in extinction retrieval, we performed an occlusion experiment in which we assessed the effects of stress alone, lesion of IL alone, and the combined effects of stress and lesion on extinction retrieval. If IL is the substrate upon which stress acts to produce deficits in extinction retrieval, then prior removal of IL should prevent the effect of stress on extinction retrieval. Rats received either sham or ibotenic acid lesions of IL. Rats in each group then remained unstressed or underwent daily restraint stress for 1week. Following the final day of restraint, rats received five habituation trials to a 30-s tone, followed by seven pairings of the tone with a 500-ms coterminating footshock. One hour later, rats received tone-alone extinction trials. On the following day, rats were given two extinction trials to test for extinction retrieval. Percent freezing was assessed throughout. Stress increased freezing during conditioning, and IL lesion did not block this effect. Either IL lesion alone or stress alone increased freezing on initial extinction trials. IL lesion did not attenuate the effect of stress during initial extinction. Similarly, IL lesion alone and stress alone produced deficits in extinction retrieval. However, stressed rats with IL lesions showed extinction retrieval comparable to that seen in unstressed, sham-lesioned rats. Thus, lesion of IL occluded the stress-induced impairment of extinction retrieval but failed to prevent the stress-induced facilitation of fear conditioning. This dissociation suggests that the effects of stress on these two aspects of emotion regulation are mediated at least in part by independent mechanisms, and that stress-induced changes in IL contribute to stress-induced deficits in extinction retrieval. [Copyright &y& Elsevier]

Abstract: Fear conditioning is accepted as a useful experimental paradigm to investigate anxious disorders following stress. In this field it is important to understand the mechanisms underlying the extinction of conditioned fear. In the rat it has been shown that the amygdalar basolateral nucleus plays a crucial role in all memorization phases of this type of memory (acquisition, consolidation, retrieval, and also reconsolidation and extinction). Recent results show that both the substantia nigra and nucleus basalis magnocellularis, two sites strongly connected with the basolateral amygdala are also involved in the consolidation of contextual fear conditioning. The aim of the present work is to investigate if latter two sites, besides the basolateral amygdala, are also involved in the extinction of the conditioned fear response. The results show that tetrodotoxin-induced inactivation of post-extinction training of either site does not impair the extinction process, which instead is impaired by inactivation of the basolateral amygdala. Thus, the present results confirm previous ones which show that diverse memorization phases (post-acquisition consolidation, extinction, reconsolidation) may be sustained by different neural sites and circuits. [ABSTRACT FROM AUTHOR]

Abstract: Past research has shown that the N-methyl-d-aspartate receptor (NMDAr) is critically involved in the extinction of learned fear in adult rats with NMDAr antagonists impairing extinction retention and NMDAr agonists enhancing it. In the present study we examined the effects of the NMDAr antagonist MK-801 on extinction in the developing rat. In Experiment 1, rats were given pairings of a white-noise conditioned stimulus (CS) and a shock unconditioned stimulus (US) on postnatal day (P)16. An extinction session, where the CS was presented without the US, occurred on P17 or P24. Prior to extinction rats were injected with MK-801 or saline. All rats were tested for fear of the CS on P25, while drug free. Saline-treated rats exhibited good retention of extinction whether they were extinguished at P17 or P25. Rats treated with MK-801 exhibited impaired extinction retention but only if extinction occurred on P24. These findings show that extinction is NMDAr-dependent at P24 but NMDAr-independent at P17. Experiment 2 further examined the involvement of NMDA receptors in extinction at different stages of development by taking advantage of a finding from several recent studies on re-extinction. These studies have shown, in adult rats, a transition from NMDAr-dependent extinction to NMDAr-independent re-extinction. That is, if rats are trained, extinguished, re-trained to the same CS, and then extinguished again (i.e., re-extinction), then NMDA receptors are not required for extinction the second time. In Experiment 2, rats were trained to fear the CS at P16; this fear was extinguished at either P17 or P24. All rats were then re-trained to fear the CS at P25, re-extinguished at P26, and tested at P27. Prior to re-extinction, rats were injected with MK-801 or saline. Rats initially extinguished at P24, an age where NMDA receptors are involved in extinction, exhibited the transition to an NMDAr-independent re-extinction process. In contrast, rats initially extinguished at P17, an age where NMDA receptors are not involved in extinction, did not (i.e., these rats still exhibited an impairment in extinction retention if given MK-801 prior to re-extinction). Taken together, these findings demonstrate that a qualitatively different system mediates extinction early in life. [Copyright &y& Elsevier]

Abstract: Appetitive contextual excitation supported by intertrial unconditioned stimuli was more easily overcome by timed conditioned responding in rats using quiet (Experiment 1) rather than noisy (Experiment 2) food pellet deliveries. Head-entry responding in acquisition peaked above the contextual baseline when pellet delivery occurred 10, 30, 60, or 90s after the onset of the 120-s white-noise conditioned stimulus (CS). Special tests in extinction revealed CS onset and offset were conditioned by pellet delivery at 0 and 120s, respectively. Responding was not undermined in Experiment 3 when noisy pellet deliveries replaced quiet pellet deliveries. Our results suggest that micro-stimuli occasioned at different times during the CS are vulnerable to overshadowing, but do not lose strength if they are already predictive. [Copyright &y& Elsevier]

Abstract: Extinction has mostly been studied in conditioning paradigms, more sparsely in spatial tasks, and never as a function of the age of a spatial memory. Using rats, we compared the time-course of extinction of a recent (5 days) vs. remote (25 days) spatial memory in a water maze, over three probe trials. When the trials were set 24h apart, performance in the remote memory group was significantly worse on the first probe trial and significantly better on the third probe trial, as compared to the recent memory group, thereby showing differences between cognitive operations underlying recent vs. remote memory extinction. In contrast, when trials were given consecutively, both groups showed a similar profile of extinction. Furthermore, in a room with overly-salient cues providing a strong remote memory trace, no difference between groups was observed when the spaced extinction paradigm was used. These results might be related to a balance between reconsolidation and extinction processes occurring after a first retrieval experience, of which the outcome may depend on the extinction protocol, and on the age and strength of a memory. [Copyright &y& Elsevier]