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PubMed1982

Failure to obtain functional equivalence between dopamine receptor blockade and extinction: evidence supporting a sensory-motor conditioning hypothesis.

The effects of pimozide were tested in a discrete trial paradigm. Following 8 days of continuous reinforcement training with a retractable bar, subjects were divided into 3 groups: Vehicle-Extinction; Pimozide-Extinction and Pimozide-Reinforcement. Pimozide rats received 1 mg/kg of drug 4 hours prior to test. On each of 3 test days reinforcement continued to be delivered on a continuous reinforcement schedule for the Pimozide-Reinforcement Group whereas it was no longer delivered for the other two groups. Each test day was separated by 4 drug-free days. The Pimozide-Reinforcement Group showed the least response suppression, followed by the Vehicle-Extinction and Pimozide-Extinction Groups. These results do not support the anhedonic hypothesis that dopamine containing neurons mediate reward processes and were interpreted within a sensory-motor conditioning framework.

Animals↗
PubMed1982

Chlordiazepoxide-induced released responding in extinction and punishment-conflict procedures is not altered by neonatal forebrain norepinephrine depletion.

The effects of chlordiazepoxide (CDZ) in extinction and punishment-conflict tasks were examined in rats after neonatal systemic administration of 6-hydroxydopamine (6-OHDA) to deplete forebrain norepinephrine (NE). At about 70 days of age the rats were water deprived and trained for three days to drink in a novel apparatus. On the fourth day (test day) drinking was either extinguished by elimination of water from the drinking tube or punished by lick-contingent shock. Just prior to this test session half of the vehicle and half of the 6-OHDA treated rats were given an injection of CDZ (8 mg/kg IP). Both the injection of CDZ and forebrain NE depletion prolonged responding during extinction and reduced the suppressant effects of punishment in male rats, and these effects were of similar magnitude. Furthermore, CDZ was as effective in neonatal 6-OHDA treated male rats as in vehicle treated rats indicating that decreased transmission is ascending NE fibers caused by CDZ is not solely responsible for its behavioral effects in extinction and conflict tasks. Rather, these effects may involve cooperative mediation by both noradrenergic and serotonergic forebrain terminals. Unexpectedly, CDZ's anti-extinction effect was absent in female rats and its anti-conflict effect observed only in NE depleted females.

Animals↗
PubMed1986

A partial reinforcement extinction effect in water-reinforced rats intermittently treated with haloperidol.

Thirsty rats were trained to traverse a straight runway for 30 sec access to water reinforcement. The experiment consisted of daily single trials during a 30-day reinforcement phase followed by 21 days of extinction. Animals that experienced no water reward on 33% of the reinforcement trials subsequently demonstrated an increased resistance to extinction of the runway response compared to continuously reinforced (CRF) animals. This "partial reinforcement extinction effect" (PREE) was also observed in CRF animals pretreated with the neuroleptic drug haloperidol (0.075 or 0.15 mg/kg) on 33% of the reinforcement trials. Thus, periodic dopamine receptor antagonism produced behavioral results comparable to those produced by periodic reward omission. These data cannot easily be accounted for by some form of general drug-induced performance deficit since the extinction trials were conducted in undrugged animals. It was concluded that dopaminergic substrates may play a role in mediating the behavioral effects of water reinforcement.

Animals↗
PubMed1990

The effects of pre- and postweaning rearing conditions on latent inhibition and partial reinforcement extinction effect in male rats.

Male rats were either handled daily or left undisturbed (nonhandled) during the first 21 days of life. At weaning (Day 22) animals in each early treatment condition were assigned to two housing conditions, isolated or grouped, creating four early/late treatment conditions: Handled-Grouped (HG), Handled-Isolated (HI), Nonhandled-Grouped (NHG), and Nonhandled-Isolated (NHI). At maturity, all animals were tested in the latent inhibition (LI, Experiment 1) and the partial reinforcement extinction effect (PREE, Experiment 2) paradigms. In LI, animals receiving prior nonreinforced preexposure to a stimulus (PE) show subsequently retarded conditioning to that stimulus as compared to nonpreexposed (NPE) controls. In the PREE, partially reinforced (PRF) animals exhibit higher resistance to extinction as compared to continuously reinforced (CRF) controls. LI and PREE were obtained in the HG condition, but were impaired in NHG and HI animals. The pattern of impairment was different in the two conditions. The absence of LI in NHG males was due to increased suppression in the PE group, whereas in HI males, was due to decreased suppression in the NPE group. Likewise, the attenuation of the PREE in NHG males stemmed primarily from decreased resistance to extinction in the PRF group, whereas in HI males, it resulted from increased resistance to extinction in the CRF group. The combination of nonhandling and isolation led to the reinstatement of both LI and PREE: normal LI and PREE were obtained in the NHI animals. These results demonstrate that early rearing experience interacts with later experience differentially depending upon the later experience.

Age Factors↗
PubMed1982

Hippocampal cellular plasticity during extinction of classically conditioned nictitating membrane behavior.

Hippocampal unit responses were recorded during extinction of classically conditioned nictitating membrane (NM) behavior in the rabbit. Prior studies have shown that during the acquisition phase of nictitating membrane conditioning, the frequency of hippocampal cell firing increases at a faster rate (across trials) than learned behavior. Results reported here show that, during the early phases of extinction, conditioned hippocampal unit responses decrement at a faster rate than learned NM behavior. Furthermore, only certain components of the conditioned hippocampal unit response display robust spontaneous recovery across successive days of extinction training. In all, results show that changes in the activity of hippocampal neurons predict changes in learned behavior over trials of conditioning and extinction, and demonstrate that hippocampal cellular activity is particularly sensitive to stimulus configurations or environmental contingencies that produce changes in behavior.

Action Potentials↗
PubMed1984

Extinction of associative learning in Hermissenda: behavior and neural correlates.

The nudibranch mollusk Hermissenda crassicornis' normal attraction to light can be suppressed by repeated pairings of light with rotation. The present study examines the effects of extinction procedures on this simple form of associative learning. Presentation of non-reinforced light steps following associative conditioning resulted in an attenuation of phototaxic suppression, evident at both short- and long-term retention intervals. The absence of habituation of phototaxic behavior, coupled with the failure to demonstrate spontaneous recovery of extinguished conditioned suppression, indicates that extinction of associative conditioning in Hermissenda depends little upon non-associative learning processes. Electrophysiological evidence indicates that the Type B photoreceptors, which have been causally implicated in the acquisition and retention of associative learning, play an important role in mediating extinction as well. Enhanced input resistances and light responses of B cells, which are produced by associative training, are absent for animals subsequently exposed to light unaccompanied by rotation. In terms of both behavioral and electrophysiological measures, extinction appears to result primarily from a reversal of the original acquisition process.

Animals↗
PubMed1990

Effects of GABAergic drugs, fornicotomy, hippocampectomy and septal lesions on the extinction of a discrete-trial fixed ratio 5 lever-press response.

The effects of certain GABA-modulating drugs, fornicotomy, hippocampectomy and various septal lesions were analysed in a discrete-trial fixed ratio 5 (FR5) bar-press paradigm. Chlordiazepoxide, fornicotomy, hippocampectomy, electrolytic lateral septal lesions and ibotenic acid medial septal lesions facilitate extinction of the FR5 response. Some of these treatments (chlordiazepoxide, hippocampectomy, electrolytic lateral septal lesions) have previously been found to increase resistance to extinction of alley-running after continuously reinforced (CRF) acquisition training. The treatments which facilitated extinction in the discrete-trial FR5 paradigm have been found to reduce or abolish the partial reinforcement extinction effect in the alley. These results indicate that the discrete-trial FR5 paradigm is not analogous to a runway CRF schedule, but may be analogous to a runway partial reinforcement schedule.

Animals↗
PubMed1983

Reduced resistance to progressive extinction in senescent rats: a neuroanatomical and behavioral study.

The behavior of senescent rats and mature-young rats was compared in a learning task which consisted of the acquisition of a visual discrimination task, its reversal, the induction of a progressively increasing extinction, relearning and, finally, a complete extinction training. It was found that young and old rats were statistically indistinguishable during all parts of the task, except the progressively increasing extinction. Here, the senescent animals made a significantly higher number of errors than the mature-young ones. Neuroanatomically, ventricular dilation, commissural changes and neuronal loss were observed in senescent rats. The significantly reduced number of neurons in the medial nucleus of the amygdala in old rats compared to young was not directly related to the changed behavior in the progressively increasing extinction part of the visual discrimination task. Based on the anatomical connections of the amygdala and its possible functions in learning and memory, the hypothesis is made that the medial amygdaloid nucleus is involved in the learning of changing response-reinforcement contingencies.

Age Factors↗
PubMed1992

Effects of early postnatal sex steroids on acquisition and extinction of a continuously reinforced lever-pressing response.

The effects of early postnatal dihydrotestosterone (DHT) and estradiol on the sexually dimorphic continuously reinforced lever-pressing response were investigated. 90-day-old male rats postnatally treated (during the first eight days of postnatal life) with cyproterone acetate (CA), tamoxifen (TX) or vehicle, and 90-day-old females treated with estradiol benzoate (EB), DHT or vehicle in the same postnatal period, were studied during the acquisition and extinction of the continuously reinforced lever-pressing response using a free-operant procedure. During acquisition, the control males made more responses per minute than the control females, and also reached the extinction criterion significantly sooner than the females. CA treatment impaired the male's performance at the levels of that shown by females, whereas TX treatment affected neither acquisition nor extinction. Inversely, in both experimental phases females treated with DHT performed like control females, whereas the acquisition and extinction performances of the EB-females were similar to those obtained in the control or TX male groups.

Androgen Antagonists↗
PubMedDate not supplied

The effects of ethanol and naloxone on extinction of jump-up avoidance performance in rats.

The present study assessed the effects of ethanol and naloxone on the extinction of a jump-up avoidance response in Sprague-Dawley rats. Rats were first trained to jump onto a shelf to escape or avoid shock (0.5 mA). Upon reaching an acquisition criterion of 8 consecutive avoidance trials, animals were removed from the apparatus and exposed to 1 of 4 doses of ethanol (0, 1.0, 2.0, or 2.5 g/kg), and either naloxone (3 mg/kg) or saline. Rats were then returned to the conditioning apparatus with the shock turned off, and resistance to extinction was assessed. Ethanol had biphasic effects with low doses (1 g/kg) facilitating, and higher doses (2 and 2.5 g/kg) suppressing number of extinction responses by comparison to controls. Naloxone did not influence the course of extinction, and did not reverse any of the effects of ethanol. These results did not support the hypothesis that the effects of ethanol on aversively-motivated behavior are opioid-mediated.

Animals↗
PubMed2006

d-Cycloserine facilitates extinction of a cocaine-induced conditioned place preference.

d-Cycloserine, a partial NMDA agonist, significantly accelerated extinction of a cocaine-induced conditioned place preference (CPP) when rats were given systemic injections immediately, but not 4h, after each extinction trial. Infusions directly into the basolateral amygdala had a similar effect. The facilitative effect of d-cycloserine on the extinction of appetitive conditioning is consistent with the idea of the formation of new learned associations during extinction.

Animals↗
PubMed2006

Contextual and temporal modulation of extinction: behavioral and biological mechanisms.

Extinction depends, at least partly, on new learning that is specific to the context in which it is learned. Several behavioral phenomena (renewal, reinstatement, spontaneous recovery, and rapid reacquisition) suggest the importance of context in extinction. The present article reviews research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval. Contexts appear to select or retrieve the current relationship of the conditional stimulus (CS) with the unconditional stimulus (US), and they are provided by physical background cues, interoceptive drug cues, emotions, recent trials, and the passage of time. The current article pays particular attention to the effects of recent trials and trial spacing. Control of fear extinction by physical context involves interactions between the dorsal hippocampus and the lateral nucleus of the amygdala. This interaction may be mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.

Amygdala↗
PubMed2006

Effects of D-cycloserine on extinction: translation from preclinical to clinical work.

Administration of benzodiazepines or serotonin reuptake inhibitors in combination with behavior therapy for the treatment of many anxiety disorders has generally lead to only modest gains. In this article we suggest that pharmacotherapy aimed not at treating the symptoms of anxiety but instead aimed at improving the learning that takes place in exposure therapy might actually improve the effectiveness of exposure therapy. This idea was based on animal work showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitated extinction of fear when given either before or shortly after exposure to fearful cues, reduced return of fear that is normally seen when extinction training is followed by stress, and led to generalized extinction, where DCS given in combination with exposure to one fearful cue led to extinction to another cue previously paired with the same aversive event. These finding suggested that DCS might facilitate exposure-based psychotherapy, which was verified in a small clinical study showing that DCS facilitated exposure therapy for fear of heights in a well-controlled virtual reality environment.

Animals↗
PubMed2006

Enhancement of hippocampal long-term potentiation induced by cocaine self-administration is maintained during the extinction of this behavior.

Drug addiction may involve learning and memory processes requiring the participation of hippocampal formation. One of the best studied examples of hippocampal synaptic plasticity is the long-term potentiation (LTP) which usually occurs when hippocampal synapses are stimulated with high-frequency stimulation. The aim of this work has been to study the effect of extinction of cocaine self-administration behavior on synaptic plasticity in rat hippocampal slices. LTP was induced using a tetanization paradigm consisting of a single train of high-frequency (100 Hz) stimulation for one second. This tetanization protocol evoked a greater and more perdurable LTP in slices obtained after 10 days of extinction of cocaine self-administration (1 mg/kg/injection) than that elicited in slices from saline self-administering (0.9% NaCl) animals. In addition, this LTP facilitation in animals which have followed the cocaine self-administration extinction protocol was very similar to that obtained in slices from cocaine self-administering animals. These results suggest that chronic cocaine self-administration induces enduring neuroadaptive changes in hippocampal synaptic plasticity which last even after the extinction of this behavior and that they may be involved in cocaine dependence.

Animals↗
PubMed2006

Stronger renewal in human fear conditioning when tested with an acquisition retrieval cue than with an extinction retrieval cue.

It was previously demonstrated in our laboratory that conditioned fear in humans can renew after extinction, when this procedure took place in a different context (ABA-renewal [Vansteenwegen et al. (2005). Return of fear in a human differential conditioning paradigm caused by a return to the original acquisition context. Behaviour Research and Therapy, 43(3), 323-336]). Using the same experimental design, we now tested the power of retrieval cues to interact with this contextual renewal phenomenon. Two groups went through acquisition and extinction (in a different context). They were then tested in the original acquisition context and in the presence of a retrieval cue. In the acquisition-cue group, this cue previously featured during the acquisition procedure; in the extinction-cue group, the cue previously featured during the extinction procedure. As expected, renewal of conditioned electro-dermal responding and retrospective expectancy ratings was strongest in the acquisition-cue group. Theoretical and clinical implications of this finding are discussed.

Association Learning↗
PubMed2005

Fear extinction in rodents: basic insight to clinical promise.

Fear extinction, the reduction of fear by repeated exposure to the object of fear, is a crucial paradigm of inhibitory learning and the acknowledged preclinical model for behavior therapy of human anxiety. Recent insights have clarified roles for infralimbic prefrontal cortex, hippocampus and periaqueductal gray in extinction learning, while maintaining a central role for the basolateral amygdaloid nucleus in the acquisition and storage of this learning. Simultaneously, molecular insights have implicated several neurotransmitter and second messenger systems in extinction learning, and revealed that extinction is surprisingly easy to improve, yielding the promise of a novel approach to improved psychiatric treatments for a variety of human anxiety disorders.

Animals↗
PubMed2005

Cannabinoid CB1 receptor is dispensable for memory extinction in an appetitively-motivated learning task.

The interaction of the cannabinoid CB1 receptor with its endogenous ligands plays an essential role in extinction of aversive memories (Marsicano, G., Wotjak, C.T., Azad, S.C., Bisogno, T., Rammes, G., Cascio, M.G., Hermann, H., Tang, J., Hofmann, C., Zieglgansberger, W., Di, M., V, Lutz, B., 2002. The endogenous cannabinoid system controls extinction of aversive memories. Nature 418, 530-534). The present study tested the generality of this observation in respect to positively-reinforced memories. To this end, male cannabinoid CB1 receptor deficient mice (CB1R-/-) and their wild-type littermate controls (CB1R+/+) were trained in an appetitively-motivated operant conditioning task, in which food-deprived animals received a food reward on nose-poking into an illuminated hole. During training, CB1R-/- turned out to be less motivated to participate in the task. After further restriction of daily food consumption, however, CB1R-/- reached the same level of performance as CB1R+/+ as far as number of correct responses and errors of omission are concerned. The accuracy of performance served as a measure for the memory of the light-reward association and was stable at similarly high levels over a retention period of 9 days without additional training (97.6+/-0.5% vs. 97.0+/-0.9% correct responses). During subsequent extinction training, the positive reinforcement was omitted. As a consequence, both CB1R-/- and CB1R+/+ showed a similar decline in accuracy of performance and total number of correct responses, accompanied by an increase in errors of omission. These data demonstrate that the cannabinoid CB1 receptor is not essential for extinction of the stimulus-response association in an appetitively-motivated learning task.

Animals↗
PubMed2006

Evaluative differential conditioning of disgust: a sticky form of relational learning that is resistant to extinction.

The present study sought to (a) test whether autonomic (i.e., electrodermal) and evaluative conditioning can be differentially established to verbal CSs, and (b) whether extinction procedures can reliably attenuate differential conditioned evaluative responding. Thirty undergraduates underwent a 10-min adaptation period followed by three consecutive conditioning phases: habituation, acquisition, and extinction. Conditioning involved participants viewing two semi-randomly presented words on a computer monitor. During acquisition, one word (CS+) was reliably paired 12 times with the UCS (pictorial stimuli depicting bodily mutilation), whereas the remaining word (CS-) was presented 12 times and reliably followed by neutral pictures (inanimate common objects). As predicted, electrodermal and evaluative responses during acquisition were of larger magnitude to the CS+ compared to the CS-. During extinction, participants continued to evaluate the CS+ as more disgusting relative to the CS-, whereas distress and fear-related emotional ratings attenuated across extinction trials. The implications of these findings for the modifiability of disgust-based evaluative responses in specific anxiety disorders will be discussed.

Adult↗