<p> A response conditioned to a specific stimulus will generalize to similar stimuli. Various reports have indicated that the slope of the gradient of generalization changes over a period of time. The experiments reported here investigated the generalization of an emotional response, originally conditioned to an 80 db. white noise to a 60 db. white noise. In different groups the tests for generalization were begun immediately after conditioning or after a 4 day waiting period. In further groups the animals' time during the delay period was variously taken up with bar pressing sessions; new conditioning trials with a light CS; unsignalled shock presentations, or they merely stayed in their home cages.</p> / Thesis / Master of Arts (MA)

<p> In six conditioned suppression experiments with rats, two conditioned stimuli (CSs) were individually trained and then tested as a compound. In one set of experiments, the suppressing effect of the compound was greater than that of either CS presented alone. This result is referred to as compound summation. In a second set of experiments, the suppressing effect of the compound was less than that of the "stronger" suppressing individual CS. This result is referred to as compound attenuation. The combination of summation and attenuation makes it possible to determine whether CSs with unknown properties are weakly excitatory (i.e., weak suppressors) or inhibitory (i.e., conditioned characteristics that are opposite the excitatory suppressing effect). If an unknown CS is tested in compound with a second CS known to be excitatory, summation indicates that the unknown stimulus is excitatory, while attenuation indicates that the unknown stimulus is inhibitory. In a final set of experiments, this compound test procedure was used to examine extinction and differential conditioning as inhibitory training procedures. Extensive extinction of a previously trained CS, even far beyond the point at which suppression vanished, was found to be an ineffective inhibitory training procedure. Rather, compound tests showed that the stimulus retained excitatory properties. Differential conditioning was found to be a very effective inhibitory training procedure, regardless of whether presentations of a previously trained CS and shock, shook alone, or the previously trained CS - alone accompanied the unreinforced CS undergoing inhibitory conditioning. These findings are discussed in terms of current theories of conditioning and unresolved issues surrounding the acquisition and maintenance of inhibitory properties.</p> / Thesis / Doctor of Philosophy (PhD)

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Made available in DSpace on 2016-04-29T13:18:11Z (GMT). No. of bitstreams: 1 Deniges Maurel Regis Neto.pdf: 596409 bytes, checksum: 66d18ae3780210e2f35957e33476f53b (MD5) Previous issue date: 2009-04-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present work intended to create some conditions for the study of the conditional suppression with human beings. Counting on seven participants, the study involved an activity in the computer in which the participants would have to click with the mouse s cursor on a small circle that moved through the screen of a computer in sessions lasting 15 minutes. Two conditions had been simultaneously presented: one produced reinforces for clicks in mouse in VI 60 s schedule of reinforcement, and another reinforcer was provided for participation in the session under FT 1 s schedule. Two arrangements had been conducted: for four participants R$0,50 were produced and accumulated in a counter presented the screen of the computer under the schedule VI 60 s and 0,01 point was accumulated in another counter under schedule FT 1 s. To the others three participants 1,00 point was produced under schedule VI 60 s for the clicks and R$0,01 was produced under schedule FT1 s. After the stabilization of the rates of responses or a maximum of four sessions, over the schedules already presented was added to the sessions an association between a tone and three events: the appearance of a person smiling and pointing in the direction of the participant, a sound of laugh (both with 3 s of duration) and the loss of 50% of the value of the reinforcement accumulated for the FT schedule (whose decrease lasted 1 s). The duration of the tone had been manipulated differently for two groups of participants. In the last session just the presentation of the tone was maintained in a respondent extinction. The data had shown to clear or occasional suppressions during the tone for four participants; two of them showed an induction of responses when the duration of the tone raised and an alteration in the stability of the suppression rates during shorter presentations of the tone / O presente trabalho pretendeu criar algumas condições para o estudo da supressão condicionada com humanos. Contando com sete participantes, o estudo envolvia uma atividade no computador na qual os participantes deveriam clicar com o cursor do mouse sobre um pequeno círculo em movimento na tela de um computador em sessões de 15 minutos. Dois reforçadores foram utilizados: um era produzido por cliques no mouse em esquema de VI 60 s, e outro reforçador era ganho ao longo da sessão esquema de FT 1 s. Dois arranjos foram criados: para quatro participantes R$0,50 eram produzidos e acumulados em um contador na tela do computador no esquema de VI 60 e 0,01 ponto era acumulado em outro contador em esquema de FT 1 s. Para outros três participantes 1,00 ponto era produzido em esquema de VI 60 s pelos cliques e R$0,01 era produzido pelo esquema de FT 1s. Após a estabilização das taxas de respostas ou um máximo de quatro sessões, era adicionado às sessões um pareamento entre um tom e três eventos: a aparição de uma pessoa sorrindo e apontando na direção do participante, um som de risada (ambos com duração de 3 s) e a perda de 50% do valor do reforço acumulado pelo esquema de FT 1s (cujo decréscimo durava 1 s). As durações do tom foram manipuladas diferentemente para dois grupos de participantes. Na sessão última sessão o pareamento era desfeito. Os dados mostraram evidentes ou ocasionais supressões de respostas durante o tom para quatro participantes; observou-se uma indução de respostas na duração mais elevada do tom e uma alteração na estabilidade das taxas de supressão durante apresentações mais curtas do tom

科学研究費補助金 研究種目:基盤研究(C) 課題番号:08610079 研究代表者:石井 澄 研究期間:1996-1998年度

L’addiction est un désordre psychobiologique caractérisé par des prises de drogue répétées, une incapacité à en contrôler la consommation et une tendance chronique à la rechute. Dans le cas des opiacés (morphine, héroïne), l’arrêt de la consommation de drogue induit un syndrome de sevrage qui peut être associé de manière forte et durable à l’environnement dans lequel il est vécu. Cette association est telle que même après une longue période d’abstinence, la simple réexposition à cet environnement peut faire émerger un état émotionnel aversif qui pourrait favoriser la rechute. Dans le cadre de la dépendance aux opiacés, il est de plus en plus clair que la réactivation des mémoires affectives associées au sevrage joue un rôle dans la motivation à rechercher de la drogue. Au plan neurobiologique, il a été montré au laboratoire que le processus de plasticité synaptique se met en place lors du conditionnement des stimuli conditionnés au sevrage des opiacés, au sein de structures limbiques impliquées à différents titres dans le processus d’apprentissage associatif. Il a été proposé que les effets de la réexposition aux stimuli conditionnés au sevrage soient dus à la réactivation spécifique de ces structures limbiques. Dans ces travaux, les stimuli environnementaux étaient associés à la fois à l’état aversif précoce du sevrage et à des symptômes somatiques, ce qui permet une première avancée dans la compréhension des processus cellulaires impliqués dans la formation et le rappel de la mémoire du sevrage. Cependant afin de mieux comprendre comment cette mémoire pourrait exercer un rôle dans la rechute, il est nécessaire d’analyser les substrats neuronaux mis en jeu de manière plus spécifique dans les effets conditionnés de la seule composante aversive précoce du sevrage. En effet, cette composante dite « motivationnelle » joue un rôle majeur chez l’individu dépendant dans le besoin de continuer à consommer la drogue, et potentiellement chez l’individu abstinent dans sa vulnérabilité à la rechute.L’objectif de mon travail de thèse a consisté à préciser les substrats neurobiologiques impliqués dans le sevrage des opiacés et dans le rappel des mémoires aversives associées notamment à la composante motivationnelle du sevrage.Dans un premier temps, nous avons développé une approche d’hybridation in situ fluorescente (catFISH) dont le principal avantage est de préciser la dynamique des activations neuronales induites par une stimulation. Nous avons validé l’utilisation du catFISH en caractérisant la dynamique d’activation neuronale dans le cortex préfrontal (CPF), le noyau accumbens (Nac), le noyau central (CeA) et basolatéral (BLA) de l’amygdale lors de la précipitation d’un syndrome de sevrage des opiacés. Nos résultats montrent que le catFISH permet de révéler des activations neuronales durables et que le CeA et le Nac présentent une dynamique d’activation différente en réponse à la précipitation du sevrage des opiacés.Dans une deuxième partie nous avons étudié les substrats neuronaux impliqués lorsque le rappel des mémoires du sevrage des opiacés exerce un effet sur un comportement opérant dirigé vers la nourriture, et ceci en fonction de l’intensité du sevrage. L’utilisation du catFISH nous a permis de différencier les activations neuronales induites par la réexposition au contexte du sevrage ou par la présentation du stimulus conditionné au sevrage. Nos résultats montrent que le CPF et le Nac shell sont impliqués dans le rappel des mémoires contextuelles du sevrage et que le CPF ainsi que le Nac core et le BLA sont activés par le rappel du stimulus conditionné au sevrage.Enfin, nous avons analysé dans un protocole d’aversion de place conditionnée les substrats neurobiologiques recrutés par le rappel des mémoires associées au syndrome de sevrage motivationnel des opiacés. Nos résultats indiquent que le Nac shell et le BLA sont les deux structures cérébrales les plus sensibles au rappel des mémoires du sevrage. L’ensemble de ce travail a permis de faire ressortir le rôle crucial du Nac shell et du BLA au sein du réseau de substrats neuronaux impliqués dans le traitement des mémoires émotionnelles aversives associées au sevrage des opiacés. Ces structures pourraient représenter les substrats communs au traitement des mémoires émotionnelles associées aux effets de drogues d’abus. L’ensemble de ces résultats devra être mis en perspective avec des travaux débutés lors de ma thèse en électrophysiologie in vivo sur animal se comportant. Ces travaux consisteront à étudier de façon longitudinale les dynamiques du réseau CPF/Nac/BLA lors de la formation et le rappel des mémoires du sevrage et permettront de mieux définir les rôles spécifiques que jouent les substrats neurobiologiques que nous avons étudiés dans le traitement des mémoires du sevrage des opiacés. / Addiction is a psychobiological disorder that is characterized by repeated drug intakes, inability to control its consumption and a chronic tendency to relapse. Concerning opiate addiction (heroin, morphine), cessation of drug consumption induces a withdrawal syndrome, which can be strongly and persistently associated with the environment in which it is experimented. This association is so tight that a single re-exposure to this specific environment is enough to provoke a negative emotional state, which may promote drug relapse. In opiate dependence, it becomes clearer and clearer that reactivation of the affective memories associated with drug withdrawal play a major role in drug seeking. In terms of neurobiological processes, previous works conducted in the lab have shown that synaptic plasticity takes place during the conditioning of stimuli to opiate withdrawal, in limbic structures known to be involved in associative learning. It has been suggested that the consequences of the re-exposition to withdrawal conditioned stimuli are due to the reactivation of these specific limbic regions. In theses studies, environmental stimuli were both associated to the early aversive state of withdrawal and to somatic symptoms. This represents a first step in the understanding of the cellular processes involved in the formation and retrieval of withdrawal memories. However, in order to better understand how these memories could play a role in relapse, it is necessary to analyze the neuronal substrates involved in the conditioned effects of the sole early aversive motivational component of opiate withdrawal. Indeed, this motivational component is considered as exerting a strong influence on the maintaining of drug consumption, and eventually on the vulnerability to relapse in abstinent addicts. The aim of my work was to specify the neurobiological substrates involved in opiate withdrawal and in the retrieval of the aversive memories especially the memories associated with the motivational component of withdrawal. We first developed an in situ hybridization approach (catFISH) whose main advantage is to add a dynamical dimension to the neuronal activations induced by a stimulation. We validated the use of the catFISH method by studying the dynamics of neuronal activations in the prefrontal cortex (PFC), the nucleus accumbens (Nac), the central (CeA) and basolateral (BLA) nucleus of the amygdala as a consequence of the precipitation of opiate withdrawal. Our results show that catFISH allows determining persistent neuronal activations and that the CeA and the Nac have a different dynamics of activation in response to opiate withdrawal. In the second part, we studied the neuronal substrates involved when the retrieval of opiate withdrawal memories modifies an operant goal-directed behaviour, according to the withdrawal intensity. The use of catFISH allowed us to differentiate the neuronal activations induced by the re-exposition to the withdrawal context or to the conditioned stimuli. Our results show that the PFC and the Nac shell are involved in the retrieval of contextual memories of withdrawal and that PFC, Nac core and BLA are activated by the retrieval of more specific conditioned stimuli.Lastly, we analysed, using a conditioned place aversion protocol, the neuronal structures recruited by the retrieval of the memories associated with the motivational component of opiate withdrawal. Our results suggest that the Nac shell and the BLA are the brain structures that are the most sensible to the retrieval of the memories of opiate withdrawal.Overall, our work emphasized the crucial role played by the Nac shell and the BLA within a network of neuronal substrates involved in the processing of aversive emotional memories associated with opiate withdrawal. These structures could be considered as the common substrates to the processing of emotional memories associated with the effects of drugs of abuse. These results will be compared with an in vivo electrophysiology on behaving animals’ approach that we initiated during my PhD. This study will consist of detailing longitudinally the dynamics of the PFC/Nac/BLA network during the formation and the retrieval of the memories of opiate withdrawal. This study will also provide more details on the specific functions of the previously studied neuronal substrates in the processing of opiate withdrawal memories.