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PubMed1978

The effects of scopolamine on extinction and spontaneous recovery.

The effects of scopolamine hydrobromide on baseline extinction levels and spontaneous recovery were assessed. Rats were trained on one of four reinforcement schedules (CRF, FR 10, FR 20, FR 40) with either food or water reinforcement. Scopolamine increased response rates in extinction and spontaneous recovery following training on all four schedules when the reinforcer was water, but had no effect on responding previously maintained by food. The results are discussed in terms of the limitations of a general theory of a cholinergic system mediating all suppressed behavior and the effects of anticholinergic drugs on central thirst mechanisms and consummatory behavior.

Animals↗
PubMed1981

Behavioural changes during withdrawal from desmethylimipramine (DMI). II. Increased resistance to extinction.

Rats withdrawn from chronic treatment with the tricyclic antidepressant desmethylimipramine (DMI) showed increased resistance to extinction in a runway and in continuously reinforced lever pressing. Changes were not seen in animals maintained on DMI. In acquisition, in the runway, there were no significant differences between groups; in the Skinner box, animals maintained on DMI performed worse than controls, but withdrawn animals recovered to control levels of performance. It is suggested that the effect on extinction may be mediated by a decrease in the efficacy of the dorsal noradrenaline bundle, which develops during chronic DMI treatment, but is masked by the presence of DMI. The implications of the conclusion for the " revised catecholamine hypothesis of depression" are discussed.

Animals↗
PubMed1977

Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion.

Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine dulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in the functional strength of amphetamine as an unconditioned stimulus.

Animals↗
PubMedDate not supplied

The role of cGMP in the extinction of the reactions of identified neurons of the edible snail in response to acetylcholine.

The possible role of cGMP in the regulation of the extinction of the reactions of the RPa4, RPa3, and LPa3 neurons of the edible snail in response to acetylcholine (ACh), applied rhythmically to the soma of the neuron by means of microiontophoresis, has been investigated. It was demonstrated that activators of guanylate cyclase which increased the level of cGMP in the cell, namely, sodium nitroprusside and sodium azide (5.10(-4)-10(-3) mole/liter), when applied intracellularly, intensify the extinction of inward transmembrane current and of depolarization of the membrane in response to ACh. The hypothesis of the participation of cGMP-dependent phosphorylation of membrane proteins in the regulation of the rate of development, depth, and duration of short-lived plasticity of the cholinoreceptors of the neuron is proposed.

Acetylcholine↗
PubMed1995

Food deprivation affects extinction and reinstatement of responding in rats.

Food deprivation has been shown to increase the self-administration of a wide variety of drugs in a number of different species. However, the effects of food deprivation on other phases of drug taking have not been established. The purpose of the present study was to evaluate the effects of food deprivation on reinstatement of responding for cocaine. Rats trained to self-administer 0.2, 0.4, or 1.0 mg/kg cocaine intravenously (IV) under a fixed-ratio 1 schedule for the first 2 h during daily 7-h sessions were fed either before or after the experimental session. During hours 3-7, rats self-administered saline. Saline replaced cocaine in the infusion pumps at the beginning of hour 3 and a priming injection of either saline or cocaine (0.32, 1.0, or 3.2 mg/kg IV) was administered at the beginning of hour 4. The number of infusions that was self-administered was measured throughout the 7-h session. During hours 1 and 2 when cocaine was available, the number of infusions was inversely related to cocaine dose. During hour 3, rats typically self-administered several infusions of saline, which gradually decreased to near-zero levels by hours 4-7 (extinction responding). A priming injection of cocaine administered at the beginning of hour 4 reinstated responding in a dose-related manner. The magnitude of extinction responding during hour 3 and reinstatement of responding during hour 4 were similar regardless of cocaine maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Nicotine reinstatement of nicotine self-administration after long-term extinction.

The effect of non-contingent priming injections of nicotine on the reinstatement of drug-seeking behaviour was studied in rats following the long-term extinction of nicotine self-administration. Male rats were trained to lever press for 0.03 mg/kg per infusion of intravenous nicotine. Nicotine maintained a robust self-administration behaviour (11.5 +/- 1.2; mean+/-SEM infusions/1-h session). When nicotine availability was discontinued, and only a non-contingent saline infusion was presented to the experimental subjects at the beginning of each daily session, responding for the drug-paired lever decreased to low values. After 4-13 sessions, responding extinguished. During this "extinction" period, non-contingent priming infusions of nicotine 0.001, 0.003, 0.01 or 0.03 mg/kg per infusion induced reinstatement of responding for the drug-paired lever. The increased responding, compared with the corresponding previous day on saline, was observed at all four nicotine doses but was not statistically significant for the higher priming dose (0.03 mg/kg per infusion). These preliminary results indicate that nicotine priming is able to induce reinstatement of drug-seeking behaviour in rats similarly to other reinforcing drugs. The present findings show analogies with similar phenomena described in ex-smokers and support the addictive role of nicotine in tobacco smoking.

Animals↗
PubMedDate not supplied

The discovery of the principles of reinforcement, extinction, generalization, and differentiation of conditional reflexes in Pavlov's laboratories.

The discovery of reinforcement, extinction, generalization, and differentiation with the conditional reflex method in Pavlov's laboratories is described. Modern American introductory texts show that contemporary understanding of the experimental work on conditioning in Pavlov's laboratories is derived from a 1927 English translation of Pavlov's lectures on the conditional reflexes. The lectures present the discoveries topically, not chronologically. In contrast, this article presents a chronological account of the contributions of S.G. Vul'fson, I.F. Tolochinov, and B.P. Babkin, which led to the conceptualization of reinforcement and extinction, and the work of V.N. Boldyrev and N.A. Kashereninova, which led to the formulation of the concepts of generalization and differentiation. This historical approach avoids giving the impression that the development of the Pavlovian paradigm was a highly systematic pursuit.

Animals↗
PubMedDate not supplied

Effects of partial reinforcement on conditioning, conditional probabilities, asymptotic performance, and extinction of the rabbit's nictitating membrane response.

Classical conditioning and extinction of the rabbit nictitating membrane response was investigated under 100 per cent, and two 50 per cent reinforcement conditions (50% equated total trials, and 50% equated reinforced trials) at average intertrial intervals (ITIs) of 30 and 60 sec. It was found that: (1) partial reinforcement reduced the rate of conditioning, but all groups eventually attained asymptomatic performance levels near 100 per cent; (2) first-order and second-order conditional probabilities following reinforced and nonreinforced trials were virtually identical; and (3) no partial reinforcement extinction effect (PREE) was observed.

Acoustic Stimulation↗
PubMedDate not supplied

Pavlovian extinction, phobias, and the limits of the cognitive paradigm.

The slow or total lack of decrease in some autonomic responses during extinction in aversive conditioning and concomitant verbalization of fear have remained a problem for learning theories and psychophysiology. Removal of the aversive stimulus should result in a rapid decrement in responding, as it does in cognitive and somatic systems. In laboratory analogues of phobia and clinical neurosis, however, such decreases do not occur in some autonomic responses and reported fear. In this article three areas of research are presented in which dissociations occur between cognitive and autonomic responses: 1) relational learning, 2) phobia, and 3) incubation. The data indicate that there are some important distinctions to be made concerning the properties of different psychological and physiological systems. These distinctions pertain to the differences between cognitive and noncognitive systems, between the two branches of the ANS, and between acquisition and extinction processes. These distinctions lead to a number of hypotheses concerning dissociations between response systems and have important implications for the understanding and treatment of neurosis.

Autonomic Nervous System↗
PubMed1997

Cytotoxic lesions of the retrohippocampal region attenuate latent inhibition but spare the partial reinforcement extinction effect.

Experiment I assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.

Analysis of Variance↗
PubMed2003

Differences between d-methamphetamine and d-amphetamine in rats: working memory, tolerance, and extinction.

RATIONALE: Previously, we have shown that d-amphetamine (AMPH) was more potent than d-methamphetamine (METH) at increasing extracellular levels of dopamine (DA) in the prefrontal cortex (PFC) at doses that had similar effects in the nucleus accumbens. Since working memory depends on PFC DA, it was postulated that AMPH would also be more potent than METH at affecting working memory. OBJECTIVE: To determine if AMPH is more potent than METH at affecting working memory. METHODS: Working memory was measured in adult female Sprague-Dawley rats using a delayed-alternation T-maze task with multiple delays (1, 10, 60 s) and food rewards. The percentage of food rewards consumed was also recorded. Animals were tested with METH and AMPH before and after a chronic protocol, with measurements of locomotor activity used to test for pharmacological tolerance or sensitization. The effects of METH and AMPH on extinction were also examined by omitting the food rewards from the T-maze. RESULTS. Both METH and AMPH produced dose-related bimodal effects on working memory at the intermediate delay (10 s); however, AMPH was more potent than METH. Both METH and AMPH initially also decreased the percentage of food rewards consumed in the T-maze. After chronic testing, animals displayed tolerance to both the working memory impairments and the reduction in food reward intake produced by AMPH. Animals did not display significant tolerance to the effects of METH on food reward consumption and performed worse in the T-maze after chronic testing. METH, but not AMPH, interfered with extinction. CONCLUSIONS: These results indicate that METH and AMPH differ in altering working memory and the expression of tolerance, perhaps due to differences in behavioral inhibition.

Amphetamines↗
PubMed2005

Reinstatement of nicotine-seeking behavior by drug-associated stimuli after extinction in rats.

RATIONALE: Smoking-related environmental stimuli have been implicated as an important factor in triggering relapse in abstinent tobacco smokers, and recent evidence indicates that drug-associated stimuli can reinstate nicotine-seeking in rats. However, there is little investigation on the factors that contribute to the latter effect. OBJECTIVE: This study examined whether a nicotine-associated visual stimulus (VS) can reinstate nicotine-seeking after extinction in a response-reinstatement model of relapse, and whether the behavioral effects of the VS are sensitive to pharmacological blockade of nicotinic neurotransmission. It also determined whether active lever reassignment after food training influences nicotine self-administration and the VS-induced reinstatement. METHODS: Male Sprague-Dawley rats were trained to self-administer nicotine (0.03 mg/kg/infusion, IV) and associate a VS with each nicotine infusion in 30 daily 1-h sessions. Half of the animals received nicotine infusions for responding at the same lever that previously delivered food; for the other half, infusions resulted from pressing the previously inactive lever during food training. Then, the nicotine-maintained response was extinguished by saline substitution and withholding the VS. One day after rats reached extinction criterion, the reinstatement tests were conducted where the VS was response-contingent represented without further delivery of nicotine. In pharmacological tests, a nicotinic antagonist, mecamylamine, was subcutaneously administered 30 min before reinstatement sessions. RESULTS: Presentation of the nicotine-associated VS significantly reinstated responding at the previously drug-reinforced lever and pretreatment with mecamylamine effectively attenuated the response-reinstating effect of the VS. Additionally, animals showed similar profiles of nicotine-taking and nicotine-seeking behavior regardless of reassignment of the active lever after food training. CONCLUSIONS: Nicotine self-administration and the VS-induced reinstatement of nicotine-seeking do not result from a lever bias due to prior experience for food reinforcement. Significantly, these results suggest that environmental stimuli associated with nicotine self-administration can effectively elicit nicotine-seeking behavior in abstinent subjects, that this effect is blocked by nicotine antagonism, and that the present procedures may be useful for studying neurobiological mechanisms of nicotine-seeking behavior and relapse.

Animals↗
PubMed2007

Conditioned effects of heroin on the expression of inducible nitric oxide synthase in the rat are susceptible to extinction and latent inhibition.

RATIONALE: The administration of heroin has been shown to inhibit the induction of nitric oxide, a molecule known to play a critical role in immune function. Previous research has shown that this alteration can be conditioned to environmental stimuli that have been associated with drug administration. However, it remains unknown whether the conditioned effects of heroin on nitric oxide formation follow accepted principles of learning. OBJECTIVE: This study sought to determine whether manipulations that induce extinction and latent inhibition, two learning paradigms known to reduce the expression of conditioned responses, would alter heroin's conditioned effects on the expression of inducible nitric oxide synthase (iNOS). MATERIALS AND METHODS: The conditioning procedure involved repeated pairing of heroin administration with placement into a standard conditioning chamber. Rats were repeatedly exposed to the chambers without heroin reinforcement to determine whether the conditioned response would extinguish. To induce latent inhibition, rats received repeated exposure to the chamber before the start of conditioning to inhibit the acquisition of the conditioned response. Ten days after the final conditioning session, all rats were injected with lipopolysaccharide (LPS) to induce iNOS expression. Spleen and liver tissue were removed to determine iNOS expression using reverse transcriptase polymerase chain reaction. Blood was collected to determine the concentration of nitrite/nitrate. RESULTS: The results showed that both extinction and latent inhibition reduced the conditioned effects of heroin on the production of nitric oxide. CONCLUSION: This study provides the first evidence that the conditioned effects of heroin on nitric oxide production follow accepted principles of learning.

Animals↗
PubMed2005

The use of visual feedback is independent of visual awareness: evidence from visual extinction.

Milner and Goodale (The visual brain in action, Oxford Press, 1995) made a distinction between vision for perception and vision for action. In contrast to perception, many action tasks have strict temporal constraints, which can only be met if the visual information is relayed directly to the motor system without first passing through a conscious decision making process. Milner and Goodale therefore predict that visual stimuli do not have to reach visual awareness in order to guide rapid motor responses. Online visual feedback provides a good example of visual information that is used under tight temporal constraints to guide rapid motor responses. Online visual feedback provides information about the position of the moving limb. This information can be used to improve the accuracy of our movements. If vision for action operates independently of visual awareness, visual feedback should be beneficial even if the subject is unaware of this information. We tested this prediction in a patient (V.E.) with left-sided visual extinction, a condition in which a visual stimulus typically fails to reach awareness if a second stimulus is presented simultaneously at a more rightward location. V.E. was asked to point towards a central target with his left hand. In some trials a light-emitting diode (LED) provided brief visual feedback from the moving hand. However, in the majority of trials, V.E. was unaware of this LED, due to his extinction. His performance was nevertheless significantly better when visual feedback was present, regardless of whether or not the information was available for verbal report. We conclude that visual awareness is not essential for the effective use of online visual feedback.

Aged↗
PubMed2006

Facilitated extinction of appetitive instrumental conditioning following excitotoxic lesions of the core or the medial shell subregion of the nucleus accumbens in rats.

The nucleus accumbens has been implicated in the control of goal-directed behaviour, including instrumental conditioning. Here, we evaluated the effect of N-methyl-D: -aspartate (NMDA)-induced excitotoxic lesions restricted to either the core or the medial shell subregions of the nucleus accumbens (NAC) on extinction in rats using a trial discrete fixed ratio-5 (FR-5) appetitive operant procedure. Neither core nor shell lesions of the NAC affected the acquisition of instrumental responding. Both lesions facilitated the cessation of responding when the instrumental act no longer yielded reinforcement. Our results suggest that both the NAC core and medial shell contribute to the control of extinction learning of appetitively motivated instrumental behaviour.

Analysis of Variance↗
PubMed1979

Noradrenaline, fear and extinction.

It has been suggested that noradrenaline in the central nervous system is involved in fear and anxiety. To test this postulate extensive depletion of ascending noradrenaline systems was accomplished by intracerebral injection of the selective neurotoxin 6-hydroxydopamine. Fear and anxiety were assessed using a Sidman avoidance task and a conditioned emotional response paradigm. No alteration in fear motivated acquisition learning of either of these tasks were detected. Resistance to extinction was seen on the conditioned emotional task, perhaps because of its continuously reinforced nature, but not on the Sidman avoidance, perhaps as a consequence of the reinforcement contingencies which render this task more similar to a partially reinforced schedule. No evidence for a role of ascending noradrenaline systems in fear or anxiety was hence obtained, but a further demonstration of a role in extinction processes was found.

Animals↗
PubMed1984

Manipulation of the amygdala noradrenergic system impairs extinction of passive avoidance.

In a consolidation paradigm, noradrenergic manipulation of the rat amygdala results in disruption of extinction for passive avoidance. These results are discussed in light of a recent controversy concerning the role of central norepinephrine systems in general extinction behavior. The discussion is cast primarily within the framework of rodent natural life history, the presence of innate behavioral strategies, and the organization of information processing as an integration of experiential attributes.

Amygdala↗
PubMed1995

Simultaneous single unit recording in the medial nucleus of the medial geniculate nucleus and amygdaloid central nucleus throughout habituation, acquisition, and extinction of the rabbit's classically conditioned heart rate.

The present study examined single neuron activity in the medial nucleus of the medial geniculate (mMG) and amygdaloid central nucleus (ACe) simultaneously across several phases of differential heart rate conditioning (habituation, acquisition, and extinction). Within the same animals, the magnitude of mMG and ACe unit responses to two tone conditioned stimuli (CS) exhibited habituation, differential acquisition, and extinction. Neurons in each area developed a differential response latency to the CSs during acquisition, suggesting that mMG and ACe may be involved in changes of synaptic efficacy. Units in both areas rapidly developed a differential response magnitude to the CSs (< 6 acquisition trials), however, mMG units responded to the CSs with a shorter latency than ACe units across all phases of training. This suggests that unlearned and learned CS information may access mMG before ACe. These results are consistent with the notion that conditioning-induced plasticity which occurs in mMG may influence the conditioning-induced plasticity that occurs further downstream in the amygdala.

Acoustic Stimulation↗