A fencanfamina (FCF) é um agonista indireto do sistema dopaminérgico que tem efeitos neurais e comportamentais similares aos observados com outras drogas estimulantes como a anfetamina ou a cocaína (COC). O presente trabalho teve como objetivo avaliar o efeito da administração aguda e repetida de FCF sobre o valor reforçador dos estímulos (Re). Foi usada a equação de igualação proposta por Herrnstein (1970) para avaliar esse efeito motivacional Foi também medido o efeito dessa droga sobre a taxa de respostas e a capacidade motora (k). Três experimentos foram realizados. Nos três experimentos o efeito da FCF foi testado em ratos treinados em um esquema múltiplo de sete componentes de diferentes Vls. Nos Experimentos 1 e 2 (E1 e E2, respectivamente) três doses agudas de FCF (0,88 mg/kg, 1,75 mg/kg e 3,5 mg/kg) foram administradas i.p. No E1 o reforçador foi água e no E2 reforçador foi sacarose. Em ambos os experimentos, o efeito da droga sobre os parâmetros estudados foi semelhante: as três doses de FCF aumentaram a taxa de respostas e diminuíram Re, sem alterar k. No Experimento 3, seis injeções de veiculo (Grupo VEI) ou de 1,75 mg/kg de FCF (Grupo DROGA) foram administradas i.p. intermitentemente aos sujeitos a fim de promover sensibilização comportamental. Após sete dias de suspensão da droga, foi administrada uma dose de 0,88 mg/kg de FCF em animais de ambos os grupos e foi medido o efeito sobre a taxa de respostas, k e Re. Os resultados obtidos mostraram que a administração repetida de FCF não alterou o efeito dessa droga sobre os parâmetros estudados. Os resultados são consistentes com os dados que mostram que a FCF tem efeitos sobre o comportamento similares aos de outros estimulantes, e apoiam a hipótese de que o aumento da taxa de respostas observado após a administração da FCF está relacionado a mudanças no valor reforçador dos estímulos, o que sugere um efeito motivacional e não motor. Além disso, os resultados sustentam as hipóteses que relacionam o sistema dopaminérgico ao processo do reforço. A falha na obtenção de sensibilização após a administração repetida de FCF poderia estar relacionada à dose utilizada ou ao numero de injeções administradas. / Fencanfamina (FCF) is an indirect dopaminergic agonist with neural and behavioral effects similar to those observed for other stimulant drugs such as the amphetamine or cocaine (COC). The aim of the present investigation was to evaluate the effect of acute and repeated administration of FCF on the reinforcing value (Re) taken as a motivational index. The Herrnstein hyperbole equation (1970) was used to evaluate this motivacional effect. The effects of FCF on response rate and motor capacity (k) where also observed. Three experiments were conducted. In all of them the effect of FCF was tested on rats trained on seven VI multiple schedule. In Experiments 1 and 2 (E1 and E2, respectively) three acute doses of FCF (0.88 mg/kg, 1.75 mg/kg and 3.5 mg/kg) were administered (i.p.) The reinforcer was water (E1) or sacarose (E2). In both experiments, the effect of the drug on the parameters studied was similar: the three doses of FCF increased the response rate, decreased Re and had no effect on k. In Experiment 3, six injections of vehicle (VEI Group) or 1.75 mg/kg of FCF (DROGA Group) were intermittently administered (i.p.) in order to promote sensitization. Seven days after drug withdrawal a single dose of 0.88 mg/kg of FCF was administered to animals in both groups and the effect on response rate, k and Re was measured. Results showed that repeated administration of FCF did not change the effect of this drug on the parameters investigated. These results are consistent with the evidence showing that FCF has behavioral effects similar to those reported for other stimulants and support the interpretation that increases in response rate are primarily related to changes in reinforcing value. Thus they probably reflect a motivational effect of the drug. Moreover, the results support the hypotheses that associate the dopaminergic system to the process of reinforcement. It is speculate that the failure to obtain sensitization after repeated administration of FCF could be related to dosage or number of injections.

There is a well-documented bidirectional relationship between pain and cognitive dysfunction, especially working memory. Despite this extensive body of research, the pain–working memory relationship is poorly understood. Pain catastrophizing – exaggerated negative cognitive and emotional responses towards pain – may contribute to working memory deficits by occupying finite, shared cognitive resources, but this has yet to be investigated. The present study sought to clarify the role of pain catastrophizing (assessed as both a trait-level disposition and state-level process) in working memory dysfunction. Healthy undergraduate participants were randomized to an ischemic pain or control task, during which they completed verbal and non-verbal working memory tests. They also completed measures of state- and trait-level pain catastrophizing. Mediation analyses indicated that state-level pain catastrophizing mediated the relationships of pain group to both verbal and non-verbal working memory, such that participants in the pain group (vs. the control group) catastrophized more about their pain, which then resulted in worse verbal and non-verbal working memory performance. In moderated mediation analyses, trait-level pain catastrophizing moderated this mediation effect for both verbal and non-verbal working memory. Those participants in the pain group who reported greater tendency to catastrophize about pain in general exhibited greater catastrophizing in-the-moment during the pain task, thereby leading to worse verbal and non-verbal working memory performance. These results provide evidence for pain catastrophizing as a putative mechanism and moderating factor of working memory dysfunction in pain. Future research should replicate these results in chronic pain samples, investigate other potential mechanisms (e.g., sleep), and develop interventions to ameliorate cognitive dysfunction by targeting pain catastrophizing.

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本研究藉由測量制約場地偏好行為及制約活動量兩種制約反應，透過制約期及後測期對藥物配對刺激之操弄，探討制約刺激與酬賞性藥物配對之歷程及其相關之神經機制。本文所使用的為低劑量(1.5 mg/kg)之安非他命，採腹腔注射方式給藥。實驗一探討後測日呈現不同的藥物配對刺激組合對兩種制約反應之影響效果，實驗結果發現受試只對與藥物配對過的兩個以上元素刺激同時出現才能引發受試表現制約場地偏好，且受試對複合刺激的活動量皆顯著高於對單一元素刺激的活動量。實驗二在制約期分別將視覺刺激與觸覺刺激與藥物配對，後測期於藥物配對箱單獨呈現視覺刺激或兩者所組成的複合刺激，測量受試兩種制約反應。實驗結果發現視覺刺激與複合刺激皆能引發制約場地偏好，受試對複合刺激的活動量亦高於對視覺刺激的活動量。實驗三則是於制約前分別破壞受試之杏仁核、背側海馬或腹側海馬，並進行實驗二之制約實驗程序。結果發現破壞杏仁核顯著的減抑單一元素刺激所引發之制約場地偏好，但不影響複合刺激引發之制約場地偏好。破壞背側海馬及腹側海馬減抑複合刺激引發之制約場地偏好。但在制約活動量表現方面，這三個腦組織均未獲得較一致性的結果。總而言之，本研究得到制約刺激之連結強度確實可以透過制約場地偏好及制約活動量反映出差異，且結果支持Rescorla-Wagner元素理論對制約刺激與非制約刺激配對歷程之假設。由破壞杏仁核及海馬對受試表現制約場地偏好造成不等程度之影響，可見杏仁核與海馬所參與以藥物配對的制約之行為功能不同。 關鍵字：心理藥物學，安非他命，制約場地偏好，制約活動，元素理論，整體理論，大白鼠 / By measuring of conditioned place preference (CPP) and conditioned locomotion, the present study manipulated various patterns of environment by composing three different contextual stimuli in the test chamber during different stages of conditioning to investigate behavioral processing and neural mechanisms underlying the association of conditioned stimulus and psychoactive drug. A relatively low dose of amphetamine (1.5 mg/kg) administered via intraperitoneal route was conducted as drug treatment throughout the study. In Experiment 1, the effects of CPP and conditioned locomotion were evaluated as different patterns of contextual stimuli composed in the test chamber presented during post-conditioning stage. The results showed CPP was significantly induced in the environment with context stimuli composed by at least two elements. And, the magnitude of conditioned locomotion induced by compound stimulus was higher than that induced by a single elemental stimulus. In Experiment 2, the effects of CPP and conditioned locomotion induced by a two-element compound stimulus were evaluated in the subjects received the drug pairing with both of each element stimulus in separate during the conditioning stage. The CPP was reliable induced by that compound stimulus. Although such CPP effect could also induced by an elemental stimulus specifically regarding to visual modality, it was not true for the other elemental stimulus manipulated on tactual modality. In Experiment 3, behavioral effects tested on the procedures of Experiment 2 were re-evaluated in the subjects received neurotoxic lesions in the amygdala, the dorsal hippocampus, or the ventral hippocampus before conditioning. While amygdaloid lesion significantly attenuated the CPP induced by elemental stimulus, such lesion did not inhibit the CPP induced by the compound stimulus. Lesions on those two hippocampal subareas disrupted the formation of CPP induced by compound stimulus. Regarding the conditioned locomotion, in contrast to what found on CPP, lesion treatment did not produce reliable effect induced by compound stimulus or elemental stimulus. In conclusion, the present findings on two conditioned responses measured support the assumption of Rescorla-Wagner Model on elemental theory. The lesion data indicate that amygdala and hippocampus are differentially involved in conditioned responses induced by psychoactive drug. Key words: psychopharmacology, amphetamine, conditioned place preference, conditioned locomotion, elemental theory, configural theory, rat.

<p>The manifestations of early sleep disturbances on cerebrospinal fluid and their relations with early developmental competencies are understudied. Recent studies highlight cerebrospinal fluid disbursement as a potential factor associated with dysfunctions in brain development. With two studies, we explored sleep and extra-axial cerebrospinal fluid (EA-CSF) connection as a potential mechanistic pathway by which sleep dysregulation influences brain and behavior development. Specifically, we evaluated associations between (1) EA-CSF to total cerebral volume (EA-CSF/TCV) ratios, (2) parent-report of child sleep problems, and (3) social communication development in typical (Study 1) and atypical populations (Study 2). In typical infants, early sleep problems did not precede later elevated EA-CSF/TCV ratios or social-communicative competence. Elevated EA-CSF/TCV ratios were associated with impaired social communication skills, suggesting that a relationship between elevated EA-CSF/TCV ratios and social communication impairments exists regardless of neurological or sleep problems. In an atypical population with autism spectrum disorder (ASD), older children with ASD had similar EA-CSF/TCV ratios to a group of their typically developing peers. Sleep problems were negatively associated with EA-CSF/TCV ratios but positively associated with social-communicative impairments for children with ASD, highlighting the influence of sleep problems on both brain and behavioral outcomes in an atypical population. In both studies, EA-CSF volumes continue to increase during early development in the typically developing populations (but not later in the atypical sample), underlining its relevance as a marker of atypical processing. Recognizing the potential roles of EA-CSF in influencing several biosocial and behavioral aspects of development, we encourage researchers to continue to explore EA-CSF growth, especially during developmental periods of flux and transition. Future work with longitudinal data can also serve to explore sleep-related developmental changes in EA-CSF, in association with behavioral and phenotypic changes. </p>