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PubMed2006

Strain and schedule-dependent differences in the acquisition, maintenance and extinction of intravenous cannabinoid self-administration in rats.

Cannabinoids have been reported to sustain self-administration in laboratory animals; however, genetic differences and environmental factors critical in the initiation and retention of such behaviour are yet to be defined. This study investigated the acquisition, maintenance and extinction of self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 (6.25-25 microg/kg/inf) in Long Evans, Lister Hooded and Sprague-Dawley rats under a continuous schedule of reinforcement and two different response-like operanda, nose-poking and lever-pressing. Results showed that Long Evans and Lister Hooded, but not Sprague Dawley, rats acquired and retained stable cannabinoid self-administration behaviour under both modus operandi, as defined by significant differences between responding in the active versus the inactive hole/lever. In rats developing firm self-administration, substitution of saline for WIN 55,212-2 extinguished the responding, supporting the notion that cannabinoids may serve as a positive reinforcer in laboratory animals. Nevertheless, significant differences among strains and responding modalities were observed in the percentage of acquisition, amount of drug intake during maintenance and timing of extinction. In addition, no significant strain differences were found in motor response to WIN 55,212-2 (0.3 and 3.0 mg/kg), thus excluding that strain differences observed during cannabinoid self-administration could be related to different cannabinoid-induced locomotor effects.

Analgesics↗
PubMed2004

Uni- and cross-modal temporal modulation of tactile extinction in right brain damaged patients.

The influence of ipsilesional tactile and visual stimuli on the ability to detect contralesional tactile stimuli was investigated in eight right brain damaged patients (RBD) with tactile extinction and in eight healthy subjects by delivering a series of single and double stimuli. Double stimuli were unimodal (tactile or visual) or cross-modal (tactile and visual) and could be delivered simultaneously or sequentially at three possible intervals (65, 125, 305 ms). In sequential double trials, left-sided stimuli preceded or followed right-sided stimuli. Subjects were asked to verbally report number (1 or 2), side (left or right) and modality (tactile, visual, visuo-tactile). Control subjects were highly accurate in detecting single and double stimuli. RBD patients detected all right-sided stimuli and left single visual or tactile stimuli with high accuracy; however, they omitted left-sided tactile stimuli in a high proportion of double trials due to the presence of tactile extinction. Omissions of left-sided tactile stimuli were minimal at the longest SOA. Moreover, at 0 and 65 ms SOA omissions were significantly higher in unimodal than in cross-modal combinations. This figure indicates that detection of contralesional tactile stimuli is modulated over time both uni- and cross-modally.

Adult↗
PubMed2006

Extinction of auditory stimuli in hemineglect: Space versus ear.

Unilateral extinction of auditory stimuli, a key feature of the neglect syndrome, was investigated in 15 patients with right (11), left (3) or bilateral (1) hemispheric lesions using a verbal dichotic condition, in which each ear received simultaneously one word, and a interaural-time-difference (ITD) diotic condition, in which both ears received both words lateralised by means of ITD. Additional investigations included sound localisation, visuo-spatial attention and general cognitive status. Five patients presented a significant asymmetry in the ITD diotic test, due to a decrease of left hemispace reporting but no asymmetry was found in dichotic listening. Six other patients presented a significant asymmetry in the dichotic test due to a significant decrease of left or right ear reporting, but no asymmetry in diotic listening. Ten of the above patients presented mild to severe deficits in sound localisation and eight signs of visuo-spatial neglect (three with selective asymmetry in the diotic and five in the dichotic task). Four other patients presented a significant asymmetry in both the diotic and dichotic listening tasks. Three of them presented moderate deficits in localisation and all four moderate visuo-spatial neglect. Thus, extinction for left ear and left hemispace can double dissociate, suggesting distinct underlying neural processes. Furthermore, the co-occurrence with sound localisation disturbance and with visuo-spatial hemineglect speaks in favour of the involvement of multisensory attentional representations.

Acoustic Stimulation↗
PubMed2005

REM sleep deprivation affects extinction of cued but not contextual fear conditioning.

Previous research has demonstrated that rapid eye movement (REM), or paradoxical, sleep deprivation can interfere with the retention of certain types of learning tasks, particularly spatial learning. The present study investigated the effects of 6 h of REM sleep deprivation on the retention and extinction of both cued and contextual conditioning tasks in rats. Sleep-deprived animals showed normal retention of both types of conditioning tasks but retarded extinction of the cued task and a trend toward attenuated spontaneous recovery of the contextual task. The results provide further evidence for the involvement of REM sleep in learning and memory processes.

Acoustic Stimulation↗
PubMed2006

Long-term evolution of an ecosystem with spontaneous periodicity of mass extinctions.

Twenty years ago, after analysing palaeontological data, Raup and Sepkoski suggested that mass extinctions on Earth appear cyclically in time with a period of approximately 26 million years (My). To explain the 26My period, a number of proposals were made involving, e.g., astronomical effects, increased volcanic activity, or the Earth's magnetic field reversal, none of which, however, has been confirmed. Here we study a spatially extended discrete model of an ecosystem and show that the periodicity of mass extinctions might be a natural feature of the ecosystem's dynamics and not the result of a periodic external perturbation. In our model, periodic changes of the diversity of an ecosystem and some of its other characteristics are induced by the coevolution of species. In agreement with some palaeontological data, our results show that the longevity of a species depends on the evolutionary stage at which the species is created. Possible further tests of our model are also discussed.

Animals↗
PubMed2004

Extinction of a conditioned response in rainbow trout selected for high or low responsiveness to stress.

Two lines of rainbow trout (Oncorhynchus mykiss) that exhibit divergent endocrine responsiveness to stressors also display disparate behavioral traits. To investigate whether the high-responding (HR) and low-responding (LR) fish also differ in cognitive function, the rate of extinction of a conditioned response was compared between the two lines. Groups of HR and LR fish were exposed to a paired conditioned stimulus (CS; water off) and unconditioned stimulus (US; confinement stressor). After exposure to 18 CS-US pairings, at least 70% of individuals of both lines acquired a conditioned response (CR) manifested as an elevation of blood cortisol levels on presentation of the CS only. Post-conditioning, the fish were tested by presentation of the CS at weekly intervals, for 4 weeks, with no further reinforcement, and the extinction of the CR in the two lines was compared. The decline in mean plasma cortisol levels after exposure to the CS over successive tests suggested that the CR was retained for a shorter period among the HR (<14 days) than LR fish (<21 days). The frequency of individuals within each line whose plasma cortisol levels indicated a stress response when exposed to the CS was significantly greater among the LR than HR fish at 14 and 21 days with no HR fish falling into this category at 21 days. At 28 days post-conditioning, there were no HR fish and only three LR fish were categorized as "stressed". These results suggest that there are differences in cognitive function between the two lines. Possible mechanisms underlying these differences are discussed.

Adaptation, Physiological↗
PubMed2000

The human cerebellum and associative learning: dissociation between the acquisition, retention and extinction of conditioned eyeblinks.

The present paper is part of a systematic exploration of the neural substrates of conditioned eyeblink responses in humans. Normal subjects and patients with lesions restricted to the cerebellum were examined for their ability to acquire new classically conditioned eyeblinks to an auditory conditioned stimulus and whether they were able to perform and extinguish a previously learned natural anticipatory eyeblink response - the kinesthetic threat eyeblink response (KTER). In classical conditioning to an auditory conditioned stimulus, cerebellar patients failed to acquire new conditioned responses. In contrast to this impairment, in the KTER task both cerebellar patients and control subjects exhibited a high incidence of anticipatory eyeblinks which were initiated before the forehead tap. These results indicate that the cerebellar circuits, which are critical for the acquisition of new conditioned responses, are not essential for the storage and expression of naturally acquired conditioned responses. In the extinction experiment, cerebellar patients failed to extinguish their KTERs. This finding suggests that in humans, the acquisition of new and the extinction of previously learned conditioned responses depends on a similar set of cerebellar circuits.

Animals↗
PubMed2003

Role of the prelimbic subregion of the medial prefrontal cortex in acquisition, extinction, and reinstatement of cocaine-conditioned place preference.

Previous research suggests that the prelimbic subregion of the medial prefrontal cortex (mPFC) is necessary for acquisition of cocaine-conditioned place preference (CPP). Recently, it has been shown that extinguished cocaine-CPP can be reinstated by cocaine priming injections, and that this effect reflects the incentive motivational effects of the cocaine prime. To determine whether the prelimbic cortex is necessary for cocaine-reinstated CPP, rats received bilateral infusions of quinolinic acid (lesion group) or vehicle (sham group) into the prelimbic cortex and were later tested for acquisition, extinction, and reinstatement of cocaine-CPP. Both sham and lesion rats exhibited robust CPP established by systemic injections of cocaine (15 mg/kg, i.p.) following either one or three drug-environment pairings. Following repeated exposure to the cocaine- and saline-paired environments, sham and lesion rats showed similar rates of extinction of cocaine-CPP. In contrast, reinstatement of cocaine-CPP by cocaine priming injections (5 and 10 mg/kg, i.p.) was attenuated in rats with prelimbic cortex lesions relative to sham controls. This finding suggests that the prelimbic cortex is involved in the incentive motivational effects of cocaine priming.

Animals↗
PubMed2001

What exactly is extinguished in unilateral visual extinction? Neurophysiological evidence.

We propose a model of unilateral visual extinction following right hemisphere lesions based on competition between contralesional and ipsilesional input to access a decision centre located in the left hemisphere. During bilateral presentations, the contralesional signal is on average less likely to activate the decision centre than the ipsilesional signal. This is because an intra-hemispheric lack of top-down attentional influences and an inter-hemispheric impairment of callosal transmission delay and/or weaken the contralesional input. Here we provide behavioural as well as event-related potential evidence for both these impairments. Finally, we argue that an essential prerequisite for contralesional extinction is the presence of a restricted general attentional capacity which often follows large right hemisphere damage.

Adolescent↗
PubMed2002

Neural response to emotional faces with and without awareness: event-related fMRI in a parietal patient with visual extinction and spatial neglect.

This study examined whether differential neural responses are evoked by emotional stimuli with and without conscious perception, in a patient with visual neglect and extinction. Stimuli were briefly shown in either right, left, or both fields during event-related fMRI. On bilateral trials, either a fearful or neutral left face appeared with a right house, and it could either be extinguished from awareness or perceived. Seen faces in left visual field (LVF) activated primary visual cortex in the damaged right-hemisphere and bilateral fusiform gyri. Extinguished left faces increased activity in striate and extrastriate cortex, compared with right houses only. Critically, fearful faces activated the left amygdala and extrastriate cortex both when seen and when extinguished; as well as bilateral orbitofrontal and intact right superior parietal areas. Comparison of perceived versus extinguished faces revealed no difference in amygdala for fearful faces. Conscious perception increased activity in fusiform, parietal and prefrontal areas of the left-hemisphere, irrespective of emotional expression; while a differential emotional response to fearful faces occurring specifically with awareness was found in bilateral parietal, temporal, and frontal areas. These results demonstrate that amygdala and orbitofrontal cortex can be activated by emotional stimuli even without awareness after parietal damage; and that substantial unconscious residual processing can occur within spared brain areas well beyond visual cortex, despite neglect and extinction.

Aged↗
PubMed1998

Manipulation of NMDA-receptor activity alters extinction of an instrumental response in rats.

The effects of pharmacologically manipulating N-methyl-D-aspartate(NMDA)-receptor activity were examined during extinction of an appetitive instrumental response in rats. After reaching acquisition criterion, subjects were treated with the antagonist dizocilpine maleate (MK801; 0.1 mg/kg), the agonist D-cycloserine (3 mg/kg), or vehicle-alone (control) and tested during a non-reinforced (extinction) session. The antagonist decreased the average number of responses occurring during the test session whereas the agonist increased the average number in contrast to controls. The effect on retention performance may be mediated by differential influence on the N-methyl-D-aspartate-dependent synaptic plasticity that occurs during associative learning. In conjunction with other studies, these data suggest that N-methyl-D-aspartate agonism may be an effective intervention for memory dysfunction.

Animals↗
PubMed2000

Heroin-specific stimuli reinstate operant heroin-seeking behavior in rats after prolonged extinction.

The clinical literature suggests that exposure to environmental stimuli previously associated with heroin availability may precipitate relapse. However, experimental studies elucidating the significance of learned associations between drug availability and reinstatement of heroin-seeking behavior in the rat are still scarce. To examine the role of environmental stimuli in reinstatement of heroin-seeking behavior, rats were trained to associate discriminative stimuli (DS+) with intravenous heroin availability vs. nonreward [i.e., availability of intravenous saline (DS-)]. The animals then were subjected to extinction training during which the discriminative stimuli were not presented, and lever pressing did not result in drug or saline infusion. The resistance to extinction varied greatly among animals (2.5-11.4 weeks). When the discriminative stimuli were reintroduced, the DS+ reinstated responding while the DS- did not. The average number of responses for heroin during the reinstatement trial (12.8) paralleled the average responding for heroin during discrimination training (12.6), suggesting that the associations between environmental stimuli and drug availability are long-lasting and powerful motivators of drug-seeking behavior.

Animals↗
PubMed1989

ACTH produces long-lasting recovery following partial extinction of an active avoidance response.

Recent data suggest that ACTH administration produces recovery of an extinguished passive avoidance response at an unusually long injection-to-test interval. The present experiment sought to explore further the durability of recovery by examining the effect of ACTH following extinction of one-way active avoidance. Adult rats were injected with 16 IU ACTH, an equivalent volume of the ACTH vehicle gel, or saline 48 h after a previously learned active avoidance response was partially extinguished. Different groups from each treatment condition were tested 15 min, 24 h, or 7 days after injection. ACTH improved avoidance performance at all injection-to-test intervals relative to saline and vehicle gel injected controls. These data indicate that unlike reversal of other types of performance decrements, in which the effect of ACTH appears to be transient, administration of the hormone following an extinction treatment can produce enduring improvement of avoidance performance.

Adrenocorticotropic Hormone↗
PubMed1989

Post-training memory facilitation blocks extinction but not retroactive interference.

Rats were trained in a step-down inhibitory avoidance task using a 0.2-mA footshock and tested 6 h later. Exposure to a session of extinction (animals placed on the box where they had been trained and left to explore it freely for 100.0 s without footshocks) or to a series of 10 tones presented in another box, in the dark, 2 h after training, hindered retention test performance. The immediate post-training ip administration of epinephrine (5.0 micrograms/kg), ACTH-(1-24) (0.2 microgram/kg), or lysine-vasopressin (10.0 micrograms/kg) facilitated retention test performance and cancelled the effect of extinction, but not the retroactive interference caused by exposure to the tones. These results support the concept that post-training facilitation induced by the hormones is due to a strengthening of the memory trace left by the avoidance task, whereas the retroactive interference caused by the tones occurs independently from that process and is more likely due to the incorporation of postevent information.

Animals↗
PubMed1992

Classical conditioning after temporal lobe lesions in man: sparing of simple discrimination and extinction.

Recent reports of impaired conditional discrimination learning in temporal lobectomy subjects have raised the question of response inhibition deficits in these patients. In the present study, left and right temporal lobectomy subjects and healthy controls completed an eyelid conditioning task, which required simple two-tone discrimination learning, followed by extinction. There were no group differences with regard to discrimination learning or extinction. General deficits in response inhibition are therefore not likely to account for the impairment in conditional discrimination observed in temporal lobectomy patients.

Acoustic Stimulation↗
PubMed2001

Elevation of prefrontal acetylcholine is related to the extinction of learned behavior in rats.

To investigate whether changes occur in acetylcholine (ACh) levels in the rat medial prefrontal cortex (mPFC) during initial lever-press extinction training, in vivo microdialysis was used to measure mPFC ACh. Elevated ACh was found during this training period. Furthermore, this elevation significantly correlated with the number of responses found in the re-training session the next day, but not with that in the initial training. These results suggest that the mPFC ACh elevation during the initial training period enhances the progress of lever-press extinction across sessions.

Acetylcholine↗
PubMed2002

Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses.

Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

Amygdala↗
PubMedDate not supplied

Prenatal cocaine effects on fear conditioning: exaggeration of sex-dependent context extinction.

Prenatal cocaine exposure results in deficits in sensory preconditioning, discrimination reversal, and spatial navigation, tasks that require input from the hippocampus. However, there are no previous studies concerning prenatal cocaine effects on contextual fear conditioning, another hippocampal-dependent task. The present experiments tested whether chronic subcutaneous administration of 40 mg/kg of cocaine HCl to pregnant rats, from gestational day (GD) 8 through 20 would lead to disruption of contextual fear conditioning in adult male and female offspring. Offspring of saline-injected/pair-fed and untreated dams served as controls. Experiment 1 used a one-trial context conditioning preparation. Rats received a 2-s, 1-mA footshock in either the test context or a novel context, or received no shock on the day prior to the no-shock test. Defecation and freezing were measures of fear. Experiment 2 used a multiple measures protocol to optimize detection of prenatal treatment effects and was preceded by an open-field test. Rats received a 2-s, 0.8-mA footshock or no shock once daily over 4 days of conditioning. During 3 days of extinction, access to an adjacent chamber enabled the observation of four additional measures of fear: side crossing, latency, nose crossing, and side-differential. There were gender-dependent effects of conditioning on freezing and the four added measures of fear. Males showed higher levels of context conditioning and extinguished more slowly than females. The measures of nose crossing and side-differential revealed that prenatal cocaine exposure exaggerated gender-specific effects of context conditioning. The effects of prenatal cocaine exposure on context extinction are sexually dimorphic.

Animals↗