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PubMedDate not supplied

Measuring the appetitive strength of ethanol: use of an extinction trial procedure.

Assessing the motivational level related to gaining access to ethanol (appetitive strength) is critical in understanding the human behavioral processes described as "craving." Use of an animal model that separates the behavior required to obtain the opportunity to consume ethanol from the actual consumption allows for independent measures of appetitive strength that are not intermixed with the effects of the consumed ethanol. In this model, two different methods have been applied to determine the appetitive strength: an across-sessions breakpoint procedure and single-session extinction trials. Although both methods provide an estimate of appetitive strength, the current studies were performed to provide some comparison between them. From the results and comparison with findings from prior studies, it was determined that the breakpoint procedure gave the most stable and potentially least influenced measure of appetitive strength. On the other hand, extinction trials in general provided a stable measure, somewhat different from breakpoint, that could be influenced by behavioral effects other than those related to ethanol consumption. Ethanol intakes were in a pharmacologically relevant range, averaging approximately 1.0 g/kg during 20 min of access to the solutions. Both the breakpoint and extinction measures provide additional evidence of a separation between the behavioral processes of ethanol seeking and ethanol drinking, as there was no relation between lever-press responding and ethanol intake. Thus, when choosing a method, it is possible to assess the appetitive strength of ethanol. However, care should be exercised to avoid misinterpretation of results.

Alcohol Drinking↗
PubMed2004

Dynamics of neural coding in the accumbens during extinction and reinstatement of rewarded behavior.

Neural correlates of reward-seeking behavior are observed in the nucleus accumbens (NAC). The dependence of these correlates upon the presence of a reward was studied by comparing the behavioral correlates observed when the presence of the reward was manipulated within a single behavioral session. Rats were well-trained on a continuous reinforcement instrumental task reinforced by 0.1 ml drops of 5% sucrose. Extracellular single-unit neural activity was recorded from electrode arrays implanted into the NAC when instrumental behavior was and then was not reinforced with sucrose (within-session extinction). A variable delay between the instrumental response and the sucrose delivery allowed for separation of neural activity related to these task events. A spike activity increase around the time of the instrumental response was the most common behavioral correlate, while a decrease in spike activity upon sucrose delivery was the second most common behavioral correlate. Following removal of the reinforcer, subjects continued to perform the instrumental response, allowing for the examination of response-related spike activity under extinction conditions in which the response was no longer reinforced by sucrose. A majority of the response-related neural activity patterns were lost when sucrose was no longer available. New neural responses also were detected during this period. For some subjects, the reinforcer was again made available during the same session. Encoding of the primary behavioral events during this period of reinstated reinforcer was similar, but not identical, to that observed during the first period of reinforced responding. These findings reveal that instrumental task-associated spike activity within the NAC is partially dependent upon the presence of the reinforcer, and that encoding across the population is distinct under reinforced and extinction conditions.

Animals↗
PubMed2006

Relationship of delay aversion and response inhibition to extinction learning, aggression, and sexual behaviour.

Impulsivity is an important symptom of many psychiatric disorders, and can be divided into two subtypes: response inhibition deficits and delay aversion. In the present study, we investigated the relationship between delay aversion and response inhibition, both to each other and to locomotion, extinction of conditioned responses, sexual behaviour, and aggressive behaviour. To that end, we quantified the behaviour of 24 rats in several tests. To measure response inhibition, rats were trained in a stop-signal task. In this operant task, rats were rewarded food if they inhibited execution of a response after presentation of an audible stop-signal. Delay aversion was measured in an operant task in which rats made a choice between a small, immediately available reward and a large reward available after a delay. The results showed that delay aversion and response inhibition were independent. Responses during extinction and various measures of aggressive behaviour were positively correlated to delay aversion. The speed of go-trials in the stop-task was correlated to non-aggressive behaviour. We conclude that the role of response inhibition in various behaviours is small, but delay aversion in particular contributes to several other behaviours, such as aggressive behaviour and extinction.

Aggression↗
PubMed2006

Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.

We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.

Adrenergic Agents↗
PubMed2006

Effects of prefeeding, intercomponent-interval food, and extinction on temporal discrimination and pacemaker rate.

This experiment investigated the effects of nonpharmacological disruption on temporal discrimination. Pigeons responded on a multiple schedule composed of fixed interval, color-matching, and temporal-discrimination components. The effects of three different disruptors (prefeeding, intercomponent-interval food, and extinction) were assessed. All disruptors decreased response rates during the fixed interval. Prefeeding and intercomponent-interval food had unsystematic effects on response patterning during the fixed interval, whereas extinction increased the relative response rate in the initial portions of the fixed interval. Accuracy of color matching was decreased by prefeeding and was not systematically affected by intercomponent-interval food and extinction. In the temporal-discrimination component, all disruptors flattened the psychophysical functions relating proportion long responses to sample duration. This result indicates a general disruption of temporal discrimination. In addition, parameter estimates derived from the behavioral theory of timing indicated all disruptors decreased pacemaker rate, a result consistent with the predictions of the theory. These results highlight the similarities between disruption of temporal discrimination by pharmacological and nonpharmacological manipulations.

Animals↗
PubMed2006

Is extinction the hallmark of operant discrimination? Reinforcement and S(Delta) effects.

Using a successive discrimination procedure with rats, three experiments investigated the contribution of reinforcement rate and amount of S(Delta) exposure on the acquisition of an operant discrimination. S(D) components and were always 2 min in length, while S(Delta) (extinction) components were either 1 min or 4 min in length; responses in S(D) were reinforced on one of four schedules. In Experiment 1, each of eight groups were exposed to one possible combination of rate of reinforcement and S(Delta) component length. At every level of reinforcement, the 4 min S(Delta) groups acquired the discrimination more quickly. However, within each level of reinforcement, the proportions of responding in S(D) as a function cumulative S(Delta) exposure were equivalent, regardless of the number of reinforcers earned in S(D), suggesting that extinction is the "hallmark" of discrimination. Experiment 2 sought to replicate these results in a within-subjects design, and although the 4 min S(Delta) conditions always produced superior discriminations, the lack of discriminated responding in some conditions suggested that stimulus disparity was reduced. Experiment 3 clarified those results and extended the finding that the acquisition of operant discrimination closely parallels extinction of responding in S(Delta). In sum, it appears that higher reinforcement rates and longer S(Delta) exposure facilitate the acquisition of discriminated operant responding.

Animals↗
PubMed2006

Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.

Amygdala↗
PubMed2005

Evidence for retarded extinction of aversive learning in anxious children.

The habituation to intense acoustic stimuli and the acquisition of differentially conditioned fear were assessed in 53 clinically anxious and 30 non-anxious control children and young adolescents. Anxious children tended to show larger electrodermal responses during habituation, but did not differ in blink startle latency or magnitude. After acquisition training, non-anxious children rated the CS+ as more fear provoking and arousing than the CS- whereas the ratings of anxious children did not differ. However, anxious children rated the CS+ as more fear provoking after extinction, a difference that was absent in non-anxious children. During extinction training, anxious children displayed larger blink magnitude facilitation during CS+ and a trend towards larger electrodermal responses, a tendency not seen in non-anxious children. These data suggest that extinction of fear learning is retarded in anxious children.

Acoustic Stimulation↗
PubMed2005

The role of extinction and reinstatement in attentional bias to threat: a conditioning approach.

We investigated the effects of extinction and reinstatement on attentional bias to fear-conditioned signals in healthy individuals using an emotional modification of a spatial cueing paradigm. Spatial cues were emotionally modulated using differential conditioning. The CS+ was sometimes followed by an aversive electrocutaneous stimulus (UCS), whereas the CS- was never followed by the UCS. During a subsequent extinction phase no UCS was presented anymore. The reinstatement phase started with one or four unpredicted UCS-only trials for half of the participants (reinstatement group). For the other half there were no additional UCS presentations (control group). We found that attention was biased to threat signals during acquisition. This biased attention largely disappeared during extinction. During the reinstatement phase attentional bias to threat signals re-emerged in the reinstatement group, but not in the control group.

Adolescent↗
PubMed2006

Concurrent excitors limit the extinction of conditioned fear in humans.

In a human fear conditioning experiment, with on-line expectancy ratings and electrodermal responding as indices of fear, two neutral stimuli (pictures of geometric shapes) were first established as reliable predictors of an electric shock. In the subsequent extinction phase, the two stimuli were repeatedly presented in compound, without the shock. The final test phase consisted of individual stimulus presentations again, which resulted in a strong return of the conditioned responses. This effect was not observed in non-conditioned control stimuli. Hence, behavioral effects of extinction seem highly specific to the stimulus constellation that has gone through the extinction procedure. We argue that pharmacological, behavioral and/or cognitive manipulations that could prevent configural processing of stimulus constellations have direct clinical potential.

Conditioning, Psychological↗
PubMed2005

The effect of a systemically active ORL-1 agonist, Ro 64-6198, on the acquisition, expression, extinction, and reinstatement of morphine conditioned place preference.

ORL-1 agonists have been proposed as potential therapeutics for substance abuse based on their propensity to counter the effects of mu opioid agonists in several systems, and to inhibit mesolimbic dopamine release, while mostly being devoid of aversive properties. In support of this, ORL-1 agonists have been shown to block the acquisition of morphine conditioned place preference (CPP). We investigated the effect of Ro 64-6198, a systemically active ORL-1 agonist, on the acquisition, expression, extinction, and reinstatement of morphine (20 mg/kg, s.c.) CPP in C57BL6/J mice. Similar to effects obtained with nociceptin/orphanin FQ, Ro 64-6198 (1 mg/kg, i.p.) blocked the acquisition of morphine CPP when given 15 min prior to each drug and vehicle conditioning session. This effect was not due to state dependent learning, since when tested again in the presence of Ro 64-6198 or vehicle no CPP was observed. Administration of Ro 64-6198 (0.3 or 1 mg/kg, i.p.) on the test day alone, in a separate group of animals, failed to block the expression of morphine CPP. Another group of mice was conditioned to morphine to develop CPP, and then exposed to the CPP chambers in the absence of drug once a day for 30 min to extinguish the CPP. Ro 64-6198 (1 mg/kg, i.p.) given 15 min prior to each session during extinction did not affect the rate of extinction. Finally, another group was conditioned to morphine, their CPP extinguished and subsequently reinstated by a priming injection of morphine (20 mg/kg, s.c.). Ro 64-6198 (1 mg/kg, i.p.), given 15 min prior to the priming injection, blocked reinstatement of morphine CPP. These results suggest that Ro 64-6198's effects may be limited to attenuation of the acute rewarding effects of morphine.

Analgesics, Opioid↗
PubMed2006

Modulation of the endogenous opioid system after morphine self-administration and during its extinction: a study in Lewis and Fischer 344 rats.

Lewis (LEW) and Fischer 344 (F344) rats show differential morphine self-administration rates. In this study, after animals of both strains self-administered morphine (1mg/kg) or extinguished this behaviour for 3, 7 or 15days, we measured the binding to, and functional state of mu opioid receptors (MORs) as well as proenkephalin (PENK) mRNA content in several brain regions. The results showed that in most brain areas: 1) LEW rats had less binding to MORs in basal conditions than F344 rats; 2) after morphine self-administration, either one of the strains or both (depending on the brain area) showed increased levels of binding to MORs as compared to basal groups; and 3) these binding levels in morphine self-administration animals came down in each extinction group. Moreover, F344 rats exhibited, in general, an increased functionality of MORs after morphine self-administration, as compared to basal groups, which also went down during extinction. Finally, the basal content of PENK mRNA was lower in LEW rats than in F344 rats and it decreased more after self-administration; during extinction, the levels of PENK mRNA got normalized in this strain. This differential modulation of the endogenous opioid system might be related to the different rates of morphine self-administration behavior exhibited by both inbred rat strains.

Analysis of Variance↗
PubMed2005

Facilitation of conditioned fear extinction by d-cycloserine is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and requires de novo protein synthesis in basolateral nucleus of amygdala.

Recent results showed that either systemic or intra-amygdala administration of d-cycloserine, a partial agonist at the glycine modulatory site on the glutamate N-methyl-d-aspartate receptor facilitates the extinction of conditioned fear. Here we evaluated the role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the effect of d-cycloserine. The facilitation effect of d-cycloserine on fear extinction and mitogen-activated protein kinase activation was completely blocked by intra-amygdala administration of mitogen-activated protein kinase inhibitor PD98059 (500 ng/side, bilaterally) or U0-126 (20 microM/side, bilaterally). Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5.0 microg/side, bilaterally) infused into the basolateral nucleus of amygdala significantly reduced both facilitation effect of d-cycloserine and phosphatidylinositol 3-kinase activation. Intra-amygdala administration of a transcription inhibitor (actinomycin D, 10 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) and a translation inhibitor (anisomycin, 125 microg dissolved in 1.6 microl vehicle; 0.8 microl per side) completely blocked the facilitation effect of d-cycloserine. Control experiments indicated the blockage by actinomycin D or anisomycin were not due to lasting damage to the basolateral nucleus of amygdala or state dependency. In addition, none of the active drugs used here altered the expression of conditioned fear. These results suggested that phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent signaling cascades and new protein synthesis within the basolateral nucleus of amygdala played important roles in the d-cycloserine facilitation of the extinction of conditioned fear.

Amygdala↗
PubMed2006

Extinction learning, reconsolidation and the internal reinforcement hypothesis.

Retrieving a consolidated memory--by exposing an animal to the learned stimulus but not to the associated reinforcement--leads to two opposing processes: one that weakens the old memory as a result of extinction learning, and another that strengthens the old, already-consolidated memory as a result of some less well-understood form of learning. This latter process of memory strengthening is often referred to as "reconsolidation", since protein synthesis can inhibit this form of memory formation. Although the behavioral phenomena of the two antagonizing forms of learning are well documented, the mechanisms behind the corresponding processes of memory formation are still quite controversial. Referring to results of extinction/reconsolidation experiments in honeybees, we argue that two opposing learning processes--with their respective consolidation phases and memories--are initiated by retrieval trials: extinction learning and reminder learning, the latter leading to the phenomenon of spontaneous recovery from extinction, a process that can be blocked with protein synthesis inhibition.

Animals↗
PubMed2006

Differences in extinction responding and reinstatement of methamphetamine-seeking behavior between Fischer 344 and Lewis rats.

Fischer 344 (F344) and Lewis (LEW) rats differ in a number of self-administration behaviors. Whether or not these strains differ in methamphetamine-primed reinstatement of extinguished responding is unknown. F344 and LEW rats were trained to self-administer intravenous (i.v.) methamphetamine (0.06 mg/kg) during daily 2-h limited access sessions for 14 days. Following methamphetamine self-administration, subjects underwent a minimum of 6 extinction sessions where responding on the previously active lever resulted in no programmed consequences. Following extinction sessions, we evaluated strain and dose dependency of methamphetamine-primed (0.06, 0.12, or 0.24 mg/kg/i.v.) reinstatement of responding. All subjects received each dose once. Dosing order was determined by utilizing a within-subjects Latin square design. We found partial strain differences in daily methamphetamine self-administration. In addition, F344 rats responded significantly more during the first extinction session compared LEW rats. Last, the LEW rats demonstrated a heightened propensity to reinstate responding following methamphetamine priming injections compared to F344 rats. Our results suggest that genetic background influences differences in methamphetamine-seeking behaviors in rats.

Animals↗
PubMed2005

Genetic sex determination and extinction.

Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

Animals↗
PubMed2006

Range retractions and extinction in the face of climate warming.

Until recently, published evidence for the responses of species to climate change had revealed more examples of species expanding than retracting their distributions. However, recent papers on butterflies and frogs now show that population-level and species-level extinctions are occurring. The relative lack of previous information about range retractions and extinctions appears to stem, at least partly, from a failure to survey the distributions of species at sufficiently fine resolution to detect declines, and from a failure to attribute such declines to climate change. The new evidence suggests that climate-driven extinctions and range retractions are already widespread.

Animals↗
PubMed2002

The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy.

Although much is now known about the neural basis of fear acquisition, the mechanisms of fear inhibition or suppression remain largely obscure. Fear inhibition is studied in the laboratory through the use of an extinction procedure, in which an animal (typically a rat) is exposed to nonreinforced presentations of a conditioned stimulus (CS; e.g., a light or tone) that had previously been paired with a fear-inducing unconditioned stimulus (US; e.g., a mild footshock). Over the course of such training, the conditioned fear response exhibited by the rat in the presence of the CS is reduced in amplitude and frequency. This procedure is analogous to those employed in the treatment of fear dysregulation in humans, which typically involve exposure to the feared object in the absence of any overt danger. Recent work on the neural basis of extinction indicates that the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are critically involved. Gamma-aminobutyric acid may act to inhibit brain areas involved in fear learning (e.g., the amygdala), and glutamate, acting at N-methyl-D-aspartate receptors, may play a role in the neural plasticity that permits this GABA-mediated inhibition to be exerted appropriately. These insights have significant implications for the conduct of extinction-based clinical interventions for fear disorders.

Amygdala↗