Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Time perception and age / Percepção do tempo e idade

ABSTRACT Our internal clock system is predominantly dopaminergic, but memory is predominantly cholinergic. Here, we examined the common sensibility encapsulated in the statement: “time goes faster as we get older”. Objective To measure a 2 min time interval, counted mentally in subjects of different age groups. Method 233 healthy subjects (129 women) were divided into three age groups: G1, 15-29 years; G2, 30-49 years; and G3, 50-89 years. Subjects were asked to close their eyes and mentally count the passing of 120 s. Results The elapsed times were: G1, mean = 114.9 ± 35 s; G2, mean = 96.0 ± 34.3 s; G3, mean = 86.6 ± 34.9 s. The ANOVA-Bonferroni multiple comparison test showed that G3 and G1 results were significantly different (P < 0.001). Conclusion Mental calculations of 120 s were shortened by an average of 24.6% (28.3 s) in individuals over age 50 years compared to individuals under age 30 years.

RESUMO Nosso sistema de relógio interno é predominantemente dopaminérgico, mas a memória é predominantemente colinérgica. Neste estudo, examinamos a assertiva comum que “o tempo passa mais rápido para pessoas mais velhas”. Objetivo Medir o intervalo de tempo 2 min contados mentalmente em pessoas de diferentes faixas etárias. Método 233 pessoas saudáveis (129 mulheres) foram divididos em três grupos: G1, 15-29 anos; G2, 30-49 anos; e G3, 50-89 anos. Foi solicitado que contassem mentalmente, com os olhos fechados, a passagem de 120 s. Resultados Os tempos aferidos foram: G1, média = 114,9 ± 35 s; G2, média = 96,0 ± 34,3 s; G3, média = 86,6 ± 34,9 s. A comparação entre os tempos de G3 e G1 (teste de comparação múltipla ANOVA-Bonferroni) foi muito significante (P < 0,001). Conclusão Cálculo mental de 120 s foi encurtado em média 24,6% (28,3 s) em pessoas maiores que 50 anos quando comparado com pessoas menores que 30 anos.

Between the foreign and the local: French midwifery, traditional practitioners, and vernacular medical knowledge about childbirth in Lima, Peru / Entre o estrangeiro e o local: obstetrizes francesas, médicos tradicionais e conhecimento médico vernáculo sobre partos em Lima, Peru

This article examines the politics of midwifery and the persecution of untitled female assistants in childbirth in early republican Peru. A close reading of late colonial publications and the works of Benita Paulina Cadeau Fessel, a French obstetriz director of a midwifery school in Lima, demonstrates both trans-Atlantic and local influences in the campaign against untitled midwives. Cadeau Fessel's efforts to promote midwifery built upon debates among writers in Peru's enlightened press, who vilified untrained midwives' and wet nurses' vernacular medical knowledge and associated them with Lima's underclass. One cannot understand the transfer of French knowledge about professional midwifery to Peru without reference to the social, political, and cultural context.

Este artigo analisa as políticas de práticas de parteiras profissionais e a condenação de parteiras leigas nos primórdios do Peru republicano. A leitura atenta de publicações de fins do período colonial e dos trabalhos de Benita Paulina Cadeau Fessel, obstetriz francesa diretora de uma escola de parteiras em Lima, revela influência tanto transatlântica como local na campanha contra as parteiras sem titulação. Cadeau Fessel promovia seu ofício com base em debates veiculados na imprensa peruana ilustrada, que aviltavam o conhecimento tradicional de amas de leite e parteiras leigas e as associavam às classes desfavorecidas. Só é possível compreender a transferência do conhecimento francês sobre trabalho de parteiras profissionais para o Peru relacionando-a ao contexto social, político e cultural.

The impact that the influenza A (H1N1) pandemic had on news reporting in the state of Paraná, Brazil / A repercussão da gripe A (H1N1) nos jornais paranaenses

This study aims to analyze how influenza A (H1N1) in 2009 was reported in the state of Paraná. A total of 189 articles were analyzed in two newspapers from Paraná. Pursuant to analysis, four themes were identified: the spread of the virus; the pandemic and fear; influenza in the health service; and influenza in public policies. By studying how influenza A was reported in the media, it was possible to see the social impact that the H1N1 pandemic represented for society, presenting challenges for public institutions and ordinary citizens, who sensed that they were in a high-risk group exposed to a potentially lethal virus. This disease radically changed the habits of a globalized community seeking to escape from vulnerability.

Este texto investiga como a gripe A (H1N1) de 2009 foi noticiada no estado do Paraná. Foram analisadas 189 matérias sobre o tema em dois jornais paranaenses, destacando-se quatro eixos: a expansão do vírus; a pandemia e o medo; a gripe no serviço de saúde; e a gripe nas políticas públicas. Por meio do estudo da repercussão da gripe A na mídia, foi possível perceber o impacto social que a pandemia H1N1 representou para a sociedade, desafiando instituições e o cidadão comum, que se percebeu dentro de um grupo de risco de uma doença noticiada como potencialmente letal. Essa doença suscitou mudanças pontuais nos hábitos de uma comunidade globalizada buscando escapar da vulnerabilidade.

How semantic deficits in schizotypy help understand language and thought disorders in schizophrenia: a systematic and integrative review / Como déficits semânticos na esquizotipia auxiliam a compreender transtornos da linguagem e do pensamento na esquizofrenia: uma revisão sistemática e integrativa

Introduction: Disorders of thought are psychopathological phenomena commonly present in schizophrenia and seem to result from deficits of semantic processing. Schizotypal personality traits consist of tendencies to think and behave that are qualitatively similar to schizophrenia, with greater vulnerability to such disorder. This study reviewed the literature about semantic processing deficits in samples of individuals with schizotypal traits and discussed the impact of current knowledge upon the comprehension of schizophrenic thought disorders. Studies about the cognitive performance of healthy individuals with schizotypal traits help understand the semantic deficits underlying psychotic thought disorders with the advantage of avoiding confounding factors usually found in samples of individuals with schizophrenia, such as the use of antipsychotics and hospitalizations. Methods: A search for articles published in Portuguese or English within the last 10 years on the databases MEDLINE, Web of Science, PsycInfo, LILACS and Biological Abstracts was conducted, using the keywords semantic processing, schizotypy and schizotypal personality disorder. Results: The search retrieved 44 manuscripts, out of which 11 were firstly chosen. Seven manuscripts were additionally included after reading these papers. Conclusion: The great majority of the included studies showed that schizotypal subjects might exhibit semantic processing deficits. They help clarify about the interfaces between cognitive, neurophysiological and neurochemical mechanisms underlying not only thought disorders, but also healthy human mind's creativity (AU)

Introdução: Transtornos do pensamento são fenômenos psicopatológicos comumente presentes na esquizofrenia e parecem resultar de déficits do processamento semântico. Traços esquizotípicos de personalidade consistem de tendências de pensamento e comportamento qualitativamente semelhantes às observadas na esquizofrenia, além de uma maior vulnerabilidade para esse transtorno. O presente trabalho teve como objetivo revisar a literatura sobre déficits de processamento semântico em amostras de indivíduos com traços esquizotípicos, discutindo o impacto desse conjunto de conhecimentos sobre a compreensão dos transtornos de pensamento na esquizofrenia. Estudos sobre o desempenho cognitivo de indivíduos saudáveis que apresentam traços esquizotípicos são úteis na elucidação dos déficits semânticos subjacentes aos transtornos psicóticos do pensamento, com a vantagem adicional de evitar fatores confundidores normalmente presentes em amostras clínicas de indivíduos esquizofrênicos, tais como uso de antipsicóticos e hospitalizações. Métodos: Foi realizada uma busca por artigos publicados em português ou inglês nos últimos 10 anos nas bases de dados MEDLINE, Web of Science, PsycINFO, LILACS e Biological Abstracts, utilizando-se as palavras-chave semantic processing, schizotypy e schizotypal personality disorder. Resultados: A pesquisa resultou em 44 manuscritos, dos quais 11 foram inicialmente selecionados. A partir da leitura desses artigos, outros sete foram adicionalmente incluídos. Conclusão: A grande maioria dos estudos incluídos mostrou que indivíduos esquizotípicos podem apresentar déficits de processamento semântico, auxiliando a compreender as interfaces cognitiva, neurofisiológica e neuroquímica subjacentes não só aos distúrbios pensamento, mas também à criatividade na mente humana saudável (AU)

Effect of epigallocatechin-3-gallate on inflammatory mediators release in LPS-induced Parkinson's disease in rats.

Degeneration of dopamine (DA)-containing neurons in the substantia nigra of the midbrain causes Parkinson's disease (PD). Although neuroinflammatory response of the brain has long been speculated to play a role in the pathogenesis of this neurological disorder, the mechanism is still poorly understood. The aim of the present study was to examine the effect of epigallocatechin-3-gallate (EGCG) in prevention of inflammatory mediators release and protection of dopaminergic neurons from lipopolysaccharide (LPS)-induced neurotoxicity. A single intraperitoneal injection of LPS (15 mg/kg) in male Sprague Dawley rats resulted in an increase of midbrain content of TNF-α, NO and a decrease of DA level at 4, 24 h, 3 and 7 days compared to the control. In addition, LPS reduced the number and the density of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the midbrain at 7 days. Pretreatment with EGCG (10 mg/kg) 24 h before LPS for 7 days decreased TNF-α and NO compared to LPS-treated rats. Moreover, it increased DA level and preserved the number and the density of TH-ir neurons compared to LPS group. In conclusion, EGCG was found to have a potential therapeutic effect against LPS-induced neurotoxicity via reducing TNF-α and NO inflammatory mediators and preserving DA level in midbrain.

Neurochemical and behavioral effects of green tea [Camellia sinensis]: a model study

Being rich in polyphenolic compounds such as flavonoids, green tea is suggested to be a potential candidate for the treatment of obesity, stress, depression, Parkinson's and other disorders. Since serotonin has an important role in the pathophysiology of these disorders, present study was designed to monitor the effects of green tea in rats. Green tea extract was provided to the male Albino Wistar rats for 5 weeks, and effects on behaviors were monitored. Results show a decrease in food intake after 5th week but not before. An increase in locomotive activities of the animals was observed, as monitored in novel as well as in familiar environment. Anxiolytic effects were observed in elevated plus maze but not in light dark activity box. An increase in dopamine and serotonin turnover was observed. Our results suggest that beneficial effects of green tea drinking might be due to alteration of serotonin and/or dopamine metabolism. We thereby propose that in further experiments, green tea should be administered in animal model of learned helplessness and effects on the development of adaptation to stress should be monitored. Neurochemical estimations of catecholamine and indoleamine in these animal models of stress exposed to green tea would help in understanding the anxiolytic effects of green tea

Association and its forensic significance between COMT gene and schizophrenia / 法医学杂志

Catechol-O-methyltransferase (COMT) gene encodes catechol-O-methyltransferase, the variant of this gene may affect the expression and metabolic activity of COMT. As the result of the changes of the effective concentration of the catecholamine neurotransmitter in the central nervous system, central nervous system dysfunctions associated with schizophrenia. This review summarizes genetic polymorphism and diversity of COMT gene. It also elaborates the relation between SNP and haplotype of COMT gene and three aspects, which including schizophrenia, attacking and violent tendency, and the frontal cognitive function of the schizophreniac. The correlativity study between genetic variation of the COMT gene and schizophrenia in patients with attacking and violent tendency may be helpful for the assessment of forensic psychiatry.

Lees' syndrome: a case series / Síndrome de Lees: uma série de casos

We report a case series of dopamine dysregulation syndrome, previously known as hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies, now designated as Lees' syndrome.

Relatamos uma série de casos da síndrome de desregulação dopaminérgica, previamente conhecida como desregulação homeostática hedonística em pacientes com doença de Parkinson em uso de terapia de reposição dopaminérgica, e agora definida como síndrome de Lees.

Dopamine promotes formation and secretion of non-fibrillar alpha-synuclein oligomers

Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of alpha-synuclein. Previous studies have suggested that DA can interact with alpha-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.

Neuroprotective effect of exogenous melatonin on dopaminergic neurons of the substantia nigra in ovariectomized rats

Melatonin has receptors in substantia nigra pars compacta [SNc] and regulates development of dopaminergic [DA] neurons. This study was undertaken to determine ability of melatonin to protect SNc dopaminergic neuron loss induced by estrogen deficiency in ovariectomized rats. Female rats were randomized into four groups of seven each: control, ethanol sham, ovariectomy [ovx] and ovx with melatonin [ovx + m]. In ovx, ovaries were removed. Ovx + m group was intraperitoneally injected with melatonin for 10 days, while the ethanol sham group received only ethanol. All rats were perfused with 4% paraformaldehyde, midbrains removed, fixed and paraffin embedded, then processed for Nissl and tyrosine hydroxylase staining [IHC]. Ten sections of SNc in Nissl and IHC staining were analyzed in each animal, Nissl stained and tyrosine hydroxylase [TH] immunoreactive cells were counted in five experimental groups randomly. Data was analyzed using SPSS by ANOVA and /-test. Differences were considered significant for P<0.05. There was less cell number in ovx compared to control and ethanol sham groups significantly [P<0.001]. The ovx + m group had more cells than the ovx group in the SNc significantly [P<0.001]. Furthermore, there was significant decrease of TH positive cell number in the ovx group compared to control and ethanol sham groups [P<0.05]. The number of TH immunoreactive cells-was higher in ovx + m compared to the ovx group [P<0.05]. These findings can be compared with human and used in clinical application for prevention of DA neuron death of SNc after ovariectomy

Use of Aripiprazole in Clozapine Induced Enuresis: Report of Two Cases

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.

CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats.

Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

Dopamine-secreting adrenal ganglioneuroma presenting with paroxysmal hypertension attacks

Adrenal ganglioneuromas are rare tumors originating from the neural crest tissue of the sympathetic nervous system. The clinical presentation for most patients is asymptomatic, and most of these tumors are hormone silent. We report a case of dopamine-secreting adrenal ganglioneuroma associated with paroxysmal hypertensive attacks in an adult patient. A 46-year-old woman was admitted to our hospital with a 2-month history of right flank pain, and a 2-year history of paroxysmal hypertensive attacks associated with headaches, palpitations, nervousness, and sweating. Abdominal CT and MRI revealed a solid round tumor approximately 4 cm in diameter on the upper pole of the right kidney. Urinary levels of dopamine and homovanillic acid were slightly elevated, although urinary levels of metanephrine and normetanephrine were suppressed. The urinary levels of epinephrine, norepinephrine, and vanillylmandelic acid were within normal limits. Right adrenalectomy was performed for treatment purposes. Histological diagnosis of the tumor was a ganglioneuroma originating from the adrenal medulla. In conclusion, this is a case of dopamine-secreting adrenal ganglioneuroma associated with paroxysmal hypertensive attacks in an adult patient

Modelagem neurocomputacional do circuito tálamo-cortical: implicações para compreensão do transtorno de défi cit de atenção e hiperatividade / A neurocomputational model for the thalamocortical loop: towards a better understanding of attention deficit hyperactivity disorder

CONTEXTO: A desatenção no transtorno de déficit de atenção e hiperatividade (TDAH) é principalmente associada à hipoatividade dopaminérgica mesocortical. Contudo, variações dopaminérgicas mesotalâmicas também afetam o controle da atenção e, possivelmente, originam alterações atencionais no TDAH. OBJETIVO: Elaboração de um modelo neurocomputacional a partir do conhecimento do funcionamento bioquímico dos sistemas dopaminérgicos mesocortical e mesotalâmico, a fim de investigar a influência dos níveis de dopamina na via mesotalâmica sobre o circuito tálamo-cortical e suas implicações nos sintomas de desatenção do TDAH. MÉTODO: Através de um conjunto de equações modelamos propriedades fisiológicas de neurônios talâmicos. A seguir, simulamos computacionalmente o comportamento do circuito tálamo-cortical variando os níveis de dopamina nas vias mesotalâmica e mesocortical. RESULTADOS: Em relação à via mesotalâmica, a hipoatividade dopaminérgica dificulta o deslocamento do foco de atenção, e a hiperatividade dopaminérgica acarreta desfocalização atencional. Quando tais situações são acompanhadas de hipoatividade dopaminérgica mesocortical, surge uma incapacidade em perceber estímulos, devido à competição sem vencedores entre regiões talâmicas pouco ativadas. A desatenção no TDAH também se origina em desequilíbrios dopaminérgicos na via mesotalâmica, que levam à focalização excessiva ou à desfocalização da atenção. CONCLUSÃO: O nosso experimento in silico sugere que no TDAH a desatenção relaciona-se com alterações dopaminérgicas, que não se restringem à via mesocortical.

BAKGROUND: Inattention symptoms observed in patients with attention deficit hyperactivity disorder (ADHD) are mostly related to a hipoactivity in the mesocortical dopaminergic pathway. However, mesothalamic dopaminergic variations also affect the attentional control, and possibly lead to attention alterations in ADHD. PURPOSE: Elaborating a neurocomputational model from biochemical knowledge of mesocortical and mesotalamic dopamine systems, to investigate how different levels of mesothalamic dopamine influence the thalamocortical loop, leading to some attention deficits observed in ADHD. METHOD: First, we model physiological properties of thalamic neurons with a set of mathematical equations. Next, we simulate computationally the modeled thalamocortical loop under different levels of mesothalamic dopamine, and also the mesocortical dopaminergic decrease. RESULTS: Low levels of mesothalamic dopamine hinders the attentional shift and, high levels of such neuromodulator lead to distraction. When such alterations occur together with a decrease in the mesocortical dopamine level, the attention deficit turns into incapacity of perceiving environmental stimuli, due to a no winner competition between low activated thalamic areas. Inattention in ADHD also has its origins in dopaminergic disturbs throughout the mesothalamic pathway, which enhance a high focusing or do not allow the attention focus consolidation. CONCLUSION: In ADHD, the inattention is related to dopaminergic alterations that are not restricted to the mesocortical system.

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.

Avances en la clínica de las adicciones: el rol del aprendizaje y la dopamina / Update in the clinic of addictions: learning and dopamine

There are two parallel explanatory models for addictions. One is the homeostatic model, that explains tolerance and the abstinence syndrome. Tolerance and abstinence are reversible phenomena that mask sensitization. These appear more commonly with the continued use of drugs, and are based in the up-regulation of cyclic AMP. The other is the plasticity model, that explains sensitization and compulsive use of drugs or addiction. Addiction is probably irreversible, underlies tolerance, appears more frequently with intermittent use of drugs, and is based in learning and memory mechanisms. Both are boldly linked to environmental and behavioral elements. In the plasticity model, dopamine (DA) has an outstanding role. Its phasic discharge is a temporal reward prediction error marker. It is the prediction error that generates learning. All the addictive drugs provoke a very strong increase of phasic DA discharge in some cerebral nuclei by direct or indirect paths. This increase is interpreted by cerebral circuits as prediction errors that generate learning behaviors. Pavlovian and operating type learning is involved. It is clinically observed as the prominence of environmental cues that are related to drug consumption, and the appearance of behaviors directed to the search and use of drugs, that are mainly involuntary and triggered by these cues. Pleasure (primary reinforcement) plays a role in this model, only in the initial stages of addiction. Understanding this double parallel model allows to design therapeutic interventions directed towards a conscious control of involuntary, environmental and affective cues that trigger drug search and use.

Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn.

Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated blood glucose level in alloxan treated animals. The extract reduced the blood sugar level raised by alloxan. Effect of alcoholic extract was also investigated on cold restraint induced stress and on scopolamine-induced memory impairment. Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers caused due to cold restraint stress were inhibited by alcoholic extract. Animals treated with alcoholic extract spent more time in open arm in elevated plus maze model. It also antagonized scopolamine induced learning and memory impairment. Baclofen induced catatonia was potentiated by alcoholic extract.

Dopamine dysregulation syndrome in Parkinson's disease: case report / Síndrome de desregulação dopaminérgica na doença de Parkinson: relato de caso

We report a 67-year-old man with Parkinson's disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.

Relatamos sobre um homem de 67 anos de idade com doença de Parkinson por 9 anos e que desenvolveu uso compulsivo de levodopa. Esse fenômeno é a principal característica da síndrome de desregulação dopaminérgica. Outros sintomas apresentados pelo paciente foram flutuações do humor e atividade de escrita aumentada, comportamento este sugestivo de punding.