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Avaliação do treino com estímulos discriminativos e condicionados sobre a autoadministração endovenosa de morfina em ratos / Discriminative and conditioned stimuli training evaluation on intravenous self-administration of morphine in ratsSerna, William Eduardo Patarroyo 28 July 2014 (has links)
Pesquisas com drogas de abuso têm mostrado consistentemente que a apresentação de estímulos ambientais associados ao uso destas substâncias pode induzir comportamentos de busca e autoadministração das mesmas. Existe a hipótese de que o controle que estímulos ambientais adquirem sobre comportamentos de autoadministração e busca por drogas de abuso poderia ser influenciado tanto pela forma de administração da droga, autoadministração (administração ativa) ou heteroadministração (administração passiva), quanto pela contingência (operante ou respondente) em que a droga foi associada com tais estímulos. Foram formados trios compostos por um sujeito de cada grupo (CONT, ACOP e VEÍC) e realizados dois experimentos. Inicialmente os sujeitos de cada trio foram acoplados por meio de caixas experimentais separadas e expostos a tentativas discretas de apresentação dos estímulos luminosos, S1 e S2, simultaneamente. Como consequência do girar a roda operante na presença de S1 por um integrante do grupo CONT, este recebia uma infusão endovenosa de morfina (0,75 mg/kg), e simultaneamente os animais acoplados no trio recebiam uma infusão de morfina na mesma dose (grupo ACOP) ou de veículo (grupo VEÍC). Posteriormente, os sujeitos de todos os grupos foram treinados a pressionar uma barra por infusões endovenosas de morfina, sem contingência discriminativa programada alguma. Para esta fase, no experimento 1, S2 esteve presente durante as sessões experimentais, porém no experimento 2, nenhum S foi apresentado. Finalmente, os estímulos S1 e S2 foram apresentados em tentativas discretas, em condições de extinção. Os resultados mostram que, durante a extinção, o desempenho dos animais do grupo CONT, mas não os dos grupos ACOP e VEÍC, foi condizente com o treino recebido inicialmente (com 80% ou mais de respostas na barra em presença de S1), indicando que foi estabelecido controle discriminativo sobre a autoadministração de morfina no treino sob a contingência operante, mas não sob a respondente. Estes resultados sugerem que comportamentos de autoadministração e busca por drogas de abuso são influenciados tanto pela forma de administração da droga, quanto pelo tipo de contingência em que uma droga é associada com estímulos ambientais / Drug abuse research has consistently shown that presentation of a drug associated with environmental stimuli can induce drug-seeking and drug-administration behaviors. It has been hypothesized that stimuli control over drug-seeking and self-administration behaviors could be influenced by drug administrations nature, self-administration (active administration) or hetero-administration (passive administration), and also influenced by the drug-stimuli association contingency (operant or respondent). Animals were exposed to right jugular vein catheterization procedure. Groups Contingent (C), Yoked (Y) and Toked Saline (YS) were formed randomly after recovery. Yoked triads were formed with one subject from each group and two experiments were executed. Initially a discriminative training (light stimuli S1 and S2 discrete trials) was presented to triads. Each time C S group member turned an instrumental wheel in presence of S1, simultaneously, an intravenous morphine infusion (0.75 mg/kg) were administrated to that subject and yoked Y group member, as well as an intravenous saline infusion was administrated to yoked YS group member, in every triad. Afterward all subjects were individually trained to lever-press for an intravenous morphine infusion with no discrimination contingency programed. In this phase, S2 was presented through sessions in Experiment 1, while in Experiment 2 no S were presented. After achieving response stability, subjects were exposed to extinction sessions. Stimuli S1 and S2 discrete trials were presented but no consequences were programed for bar-press responses. Results show that only C groups performance was consistent with the previously received discriminative training (80% or more of bar-press responses in S1 presence) during extinction sessions, indicating that an operant training, but not a respondent training, successfully established morphine self-administration discriminative control. These results suggest that self-administration behaviors are in fact influenced by drugs administration nature and also by the drug-stimuli association contingency
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Avaliação do treino com estímulos discriminativos e condicionados sobre a autoadministração endovenosa de morfina em ratos / Discriminative and conditioned stimuli training evaluation on intravenous self-administration of morphine in ratsWilliam Eduardo Patarroyo Serna 28 July 2014 (has links)
Pesquisas com drogas de abuso têm mostrado consistentemente que a apresentação de estímulos ambientais associados ao uso destas substâncias pode induzir comportamentos de busca e autoadministração das mesmas. Existe a hipótese de que o controle que estímulos ambientais adquirem sobre comportamentos de autoadministração e busca por drogas de abuso poderia ser influenciado tanto pela forma de administração da droga, autoadministração (administração ativa) ou heteroadministração (administração passiva), quanto pela contingência (operante ou respondente) em que a droga foi associada com tais estímulos. Foram formados trios compostos por um sujeito de cada grupo (CONT, ACOP e VEÍC) e realizados dois experimentos. Inicialmente os sujeitos de cada trio foram acoplados por meio de caixas experimentais separadas e expostos a tentativas discretas de apresentação dos estímulos luminosos, S1 e S2, simultaneamente. Como consequência do girar a roda operante na presença de S1 por um integrante do grupo CONT, este recebia uma infusão endovenosa de morfina (0,75 mg/kg), e simultaneamente os animais acoplados no trio recebiam uma infusão de morfina na mesma dose (grupo ACOP) ou de veículo (grupo VEÍC). Posteriormente, os sujeitos de todos os grupos foram treinados a pressionar uma barra por infusões endovenosas de morfina, sem contingência discriminativa programada alguma. Para esta fase, no experimento 1, S2 esteve presente durante as sessões experimentais, porém no experimento 2, nenhum S foi apresentado. Finalmente, os estímulos S1 e S2 foram apresentados em tentativas discretas, em condições de extinção. Os resultados mostram que, durante a extinção, o desempenho dos animais do grupo CONT, mas não os dos grupos ACOP e VEÍC, foi condizente com o treino recebido inicialmente (com 80% ou mais de respostas na barra em presença de S1), indicando que foi estabelecido controle discriminativo sobre a autoadministração de morfina no treino sob a contingência operante, mas não sob a respondente. Estes resultados sugerem que comportamentos de autoadministração e busca por drogas de abuso são influenciados tanto pela forma de administração da droga, quanto pelo tipo de contingência em que uma droga é associada com estímulos ambientais / Drug abuse research has consistently shown that presentation of a drug associated with environmental stimuli can induce drug-seeking and drug-administration behaviors. It has been hypothesized that stimuli control over drug-seeking and self-administration behaviors could be influenced by drug administrations nature, self-administration (active administration) or hetero-administration (passive administration), and also influenced by the drug-stimuli association contingency (operant or respondent). Animals were exposed to right jugular vein catheterization procedure. Groups Contingent (C), Yoked (Y) and Toked Saline (YS) were formed randomly after recovery. Yoked triads were formed with one subject from each group and two experiments were executed. Initially a discriminative training (light stimuli S1 and S2 discrete trials) was presented to triads. Each time C S group member turned an instrumental wheel in presence of S1, simultaneously, an intravenous morphine infusion (0.75 mg/kg) were administrated to that subject and yoked Y group member, as well as an intravenous saline infusion was administrated to yoked YS group member, in every triad. Afterward all subjects were individually trained to lever-press for an intravenous morphine infusion with no discrimination contingency programed. In this phase, S2 was presented through sessions in Experiment 1, while in Experiment 2 no S were presented. After achieving response stability, subjects were exposed to extinction sessions. Stimuli S1 and S2 discrete trials were presented but no consequences were programed for bar-press responses. Results show that only C groups performance was consistent with the previously received discriminative training (80% or more of bar-press responses in S1 presence) during extinction sessions, indicating that an operant training, but not a respondent training, successfully established morphine self-administration discriminative control. These results suggest that self-administration behaviors are in fact influenced by drugs administration nature and also by the drug-stimuli association contingency
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Effects of reinforcer density versus reinforcement schedule on human behavioral momentumSlivinski, James G. 30 March 2009 (has links)
The essential tenet of the behavioral momentum model (BMM) is that relative response rate decreases less in the face of disruption when maintained by a higher reinforcer density. Empirical support exists based on both response-dependent and response-independent reinforcement. In the present study the BMM was tested with college students in 4 multi-element experiments, each using 2 reinforcement schedules and a disrupter. Participants performed a categorical sort (by orientation) of triangles on a computer monitor. Sorting response rates were disrupted by a concurrent task, pressing the keyboard “T” key whenever 2 displayed changing numbers were equal. Initial training established fast (under VR 4) and slow (under DRL 5-s) sorting rates, and provided practice with the disrupting task. In Experiment 1 DRL 5-s provided higher reinforcer density, while in Experiment 2 VR 4 did. In Experiment 3 the higher total reinforcer density was achieved by adding VT 6-s to DRL 5-s while in Experiment 4 it was achieved by adding VT 12-s to VR 4. In all 4 experiments, sorting rate decreased with introduction of the disrupter. In Experiments 1 and 3, relative sorting rate decreased less under DRL based schedule (greater reinforcer density), supporting the BMM. However, in Experiments 2 and 4, relative sorting also decreased less under DRL (lower reinforcer density), contrary to the BMM prediction. Taken together, these data show greater relative resistance to change under DRL (versus VR), independent of reinforcer density. Thus, contrary to the BMM, the nature of the reinforcement schedule seemed to be the principal factor determining behavioral momentum. / May 2009
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Le conditionnement classique de la réponse sexuelle humaine masculineDe Gagné, Richard January 2007 (has links)
Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal
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Effects of reinforcer density versus reinforcement schedule on human behavioral momentumSlivinski, James G. 30 March 2009 (has links)
The essential tenet of the behavioral momentum model (BMM) is that relative response rate decreases less in the face of disruption when maintained by a higher reinforcer density. Empirical support exists based on both response-dependent and response-independent reinforcement. In the present study the BMM was tested with college students in 4 multi-element experiments, each using 2 reinforcement schedules and a disrupter. Participants performed a categorical sort (by orientation) of triangles on a computer monitor. Sorting response rates were disrupted by a concurrent task, pressing the keyboard “T” key whenever 2 displayed changing numbers were equal. Initial training established fast (under VR 4) and slow (under DRL 5-s) sorting rates, and provided practice with the disrupting task. In Experiment 1 DRL 5-s provided higher reinforcer density, while in Experiment 2 VR 4 did. In Experiment 3 the higher total reinforcer density was achieved by adding VT 6-s to DRL 5-s while in Experiment 4 it was achieved by adding VT 12-s to VR 4. In all 4 experiments, sorting rate decreased with introduction of the disrupter. In Experiments 1 and 3, relative sorting rate decreased less under DRL based schedule (greater reinforcer density), supporting the BMM. However, in Experiments 2 and 4, relative sorting also decreased less under DRL (lower reinforcer density), contrary to the BMM prediction. Taken together, these data show greater relative resistance to change under DRL (versus VR), independent of reinforcer density. Thus, contrary to the BMM, the nature of the reinforcement schedule seemed to be the principal factor determining behavioral momentum.
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Effects of reinforcer density versus reinforcement schedule on human behavioral momentumSlivinski, James G. 30 March 2009 (has links)
The essential tenet of the behavioral momentum model (BMM) is that relative response rate decreases less in the face of disruption when maintained by a higher reinforcer density. Empirical support exists based on both response-dependent and response-independent reinforcement. In the present study the BMM was tested with college students in 4 multi-element experiments, each using 2 reinforcement schedules and a disrupter. Participants performed a categorical sort (by orientation) of triangles on a computer monitor. Sorting response rates were disrupted by a concurrent task, pressing the keyboard “T” key whenever 2 displayed changing numbers were equal. Initial training established fast (under VR 4) and slow (under DRL 5-s) sorting rates, and provided practice with the disrupting task. In Experiment 1 DRL 5-s provided higher reinforcer density, while in Experiment 2 VR 4 did. In Experiment 3 the higher total reinforcer density was achieved by adding VT 6-s to DRL 5-s while in Experiment 4 it was achieved by adding VT 12-s to VR 4. In all 4 experiments, sorting rate decreased with introduction of the disrupter. In Experiments 1 and 3, relative sorting rate decreased less under DRL based schedule (greater reinforcer density), supporting the BMM. However, in Experiments 2 and 4, relative sorting also decreased less under DRL (lower reinforcer density), contrary to the BMM prediction. Taken together, these data show greater relative resistance to change under DRL (versus VR), independent of reinforcer density. Thus, contrary to the BMM, the nature of the reinforcement schedule seemed to be the principal factor determining behavioral momentum.
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Pavlovian-to-Instrumental Transfer in Alcohol Dependence: A Pilot StudyGarbusow, Maria, Schad, Daniel J., Sommer, Christian, Jünger, Elisabeth, Sebold, Miriam, Friedel, Eva, Wendt, Jean, Kathmann, Norbert, Schlagenhauf, Florian, Zimmermann, Ulrich S., Heinz, Andreas, Huys, Quentin J. M., Rapp, Michael A. 04 August 2020 (has links)
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping ongoing thought and behavior. The influence of pavlovian stimuli on ongoing behavior is paradigmatically measured by pavlovian-to-instrumental transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced PIT. Methods: Thirty-two recently detoxified alcohol-dependent patients and 32 age- and gender-matched healthy controls performed a PIT task with instrumental go/no-go approach behaviors. The task involved both pavlovian stimuli associated with monetary rewards and losses, and images of drinks. Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect, and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs. Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol-dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
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Neural mechanisms and pharmacological modulation of Pavlovian learningEbrahimi, Claudia 05 March 2021 (has links)
Einige psychische Störungen, darunter Angst- und Suchterkrankungen, zeichnen sich durch eine abnorme Beteiligung basaler assoziativer Lernprozesse aus. Pawlow’sche Rückfallphänomene den langfristigen Erfolg extinktionsbasierter Therapien. Damit kommt der Untersuchung pharmakologischer Interventionen zur Unterstützung des Extinktionslernens bzw. -abrufs eine zentrale Bedeutung zu.
Die vorliegende Dissertation umfasst vier Studien und bedient sich translationaler Pawlow’scher Lernmodelle, um (i) behaviorale und neuronale Mechanismen appetitiver Pawlow’scher Rückfallphänomene beim Menschen zu untersuchen (Studien I und II) sowie (ii) den Effekt des partiellen NMDA Rezeptor Agonisten D-Cycloserin (DCS) zur Unterstützung des Extinktionslernens appetitiver und aversiver Stimuli zu testen (Studien III und IV).
Studie I demonstriert, dass appetitive Pawlow’sche Rückfalleffekte im Labor untersucht werden können und lieferte Evidenz für differenzielle Einflüsse der Amygdala und des vmPFC beim Wiederauftreten der konditionierten Reaktion. Studie II belegt die Sensitivität verschiedener, teilweise neuer okularer Reaktionsmaße für die appetitive Konditionierungsforschung. Studie III zeigte, dass DCS mit einer attenuierten BOLD-Antwort in der Amygdala und einer gesteigerten funktionellen Amygdala-vmPFC Konnektivität während des appetitiven Extinktionsabrufs assoziiert war. Studie IV ergab, dass Probanden der DCS- Gruppe attenuierte Arousal Ratings wie auch neuronale Aktivierungen in der Amygdala und dem posterioren Hippocampus im Vergleich zur Placebo-Gruppe aufwiesen.
Die vorliegende Arbeit erweitert unser Verständnis appetitiver Pawlow’scher Rückfallphänomene und weist dem vmPFC eine bedeutsame Rolle beim Extinktionsabruf zu. Weiterhin unterstützt sie die Hypothese, dass DCS das Extinktionslernen unterstützt und damit Rückfallphänomene reduziert. / Pavlovian learning mechanisms play an important role in the development, maintenance, and relapse of psychiatric conditions like drug addiction and anxiety disorders. Pavlovian relapse phenomena challenge the long-term success of extinction-based exposure treatments. As such, investigating pharmacological adjuncts that could help to improve extinction learning or long- term retention are of great clinical importance.
This dissertation comprises four studies applying translational human laboratory models of Pavlovian learning (i) to characterize the behavioral and neural mechanisms of appetitive Pavlovian relapse (Studies I and II), and (ii) to investigate D-cycloserine (DCS), a partial NMDA receptor agonist, as a pharmacological adjunct to augment Pavlovian extinction learning of appetitive and aversive stimuli (Studies III and IV).
In Study I, we showed that appetitive Pavlovian relapse can be successfully modeled in the laboratory and provided evidence for opposing roles of amygdala and vmPFC in mediating the return of conditioned responding. Study II showed the usefulness of different and partly novel ocular response measures for appetitive conditioning research. Finally, we found DCS to attenuate amygdala reactivity during appetitive extinction recall and enhance amygdala-vmPFC coupling (Study III). Corroborating these results, Study IV showed DCS to reduce return of fear on behavioral arousal ratings and in brain areas associated with defense reactions like amygdala and posterior hippocampus.
Overall, the present work extends evidence on experimentally induced return of fear to the appetitive research domain and suggests an overarching regulatory role of the vmPFC during extinction recall. Finally, it supports the hypothesis that DCS can augment extinction learning, thereby reducing the risk of relapse phenomena.
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Development of Novel Tasks to Assess Outcome-Specific and General Pavlovian-to-Instrumental Transfer in HumansBelanger, Matthew J., Chen, Hao Chen, Hentschel, Angela, Garbusow, Maria, Ebrahimi, Claudia, Knorr, Felix G., Zech, Hilmar G., Pilhatsch, Maximilian, Heinz, Andreas, Smolka, Michael N. 22 February 2024 (has links)
Introduction: The emergence of Pavlovian-to-instrumental transfer (PIT) research in the human neurobehavioral domain has been met with increased interest over the past two decades. A variety of PIT tasks were developed during this time; while successful in demonstrating transfer phenomena, existing tasks have limitations that should be addressed. Herein, we introduce two PIT paradigms designed to assess outcome-specific and general PIT within the context of addiction. - Materials and Methods: The single-lever PIT task, based on an established paradigm, replaced button presses with joystick motion to better assess avoidance behavior. The full transfer task uses alcohol and nonalcohol rewards associated with Pavlovian cues and instrumental responses, along with other gustatory and monetary rewards. We constructed mixed-effects models with the addition of other statistical analyses as needed to interpret various behavioral measures.- Results: Single-lever PIT: both versions were successful in eliciting a PIT effect (joystick: p < 0.001, ηp² = 0.36, button-box: p < 0.001, ηp ² = 0.30). Full transfer task: it was determined that the alcohol and nonalcoholic reward cues selectively primed their respective reward-associated responses (gustatory version: p < 0.001, r = 0.59, and monetary version: p < 0.001, r = 0.84). The appetitive/aversive cues resulted in a general transfer effect (gustatory: p < 0.001, ηp² = 0.09, and monetary: p < 0.001, ηp ² = 0.17). - Discussion/Conclusion: Single-lever PIT: PIT was observed in both task versions. We posit that the use of a joystick is more advantageous for the analysis of avoidance behavior. It evenly distributes movement between approach and avoid trials, which is relevant to analyzing fMRI data. Full transfer task: While gustatory conditioning has been used in the past to elicit transfer effects, we present the first paradigm that successfully elicits both specific and general transfers in humans with gustatory alcohol rewards.
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Susceptibility to interference between Pavlovian and instrumental control predisposes risky alcohol use developmental trajectory from ages 18 to 24Chen, Hao, Belanger, Matthew J., Garbusow, Maria, Kuitunen-Paul, Sören, Huys, Quentin J. M., Heinz, Andreas, Rapp, Michael A., Smolka, Michael N. 05 March 2024 (has links)
Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-toinstrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.
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