RESUMO
Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 âmM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 âmM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 âmM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.
Assuntos
Drosophila melanogaster/embriologia , Hipercinese/fisiopatologia , Sobrecarga de Ferro/embriologia , Animais , Comportamento Animal/fisiologia , Aminas Biogênicas/metabolismo , Aminas Biogênicas/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Hipercinese/etiologia , Ferro/metabolismo , Ferro/fisiologia , Ferro/toxicidade , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/fisiopatologia , Locomoção/efeitos dos fármacos , Masculino , Exposição Materna , Atividade Motora/efeitos dos fármacos , Oxirredução , Exposição PaternaRESUMO
The olfactory bulbectomy (OB) animal model of depression is a well-established model that is capable of detecting antidepressant activity following chronic drug therapy, and the surgery results in behavioral and biochemical changes that are reminiscent of various symptoms of depression. In the present study, we investigated the degree to which 14 days of p.o. administration of the classic antidepressant fluoxetine (10mg/kg) were able to reverse OB-induced changes in behavior (namely, hyperactivity in the open-field test and reduced motivational and self-care behaviors in the splash test) and in the activation of hippocampal cell signaling pathways that are thought to be involved in synaptic plasticity. OB caused significant increases in ERK1 and CREB (Ser(133)) phosphorylation and in the expression of BDNF immunocontent, all of which were prevented by fluoxetine administration. Moreover, fluoxetine administration also caused a significant decrease in ERK2 phosphorylation in mice that had undergone OB. Neither Akt nor GSK-3ß phosphorylation was altered in any experimental condition. In conclusion, the present study shows that OB can induce significant behavioral changes that are accompanied by the activation of hippocampal signaling pathways, namely the ERK1/CREB/BDNF pathway, which is involved in the synaptic plasticity. Conversely, fluoxetine prevented these OB-induced behavioral changes and avoided the activation of ERK1/CREB/BDNF in the hippocampus. Taken together, our results extend the data from the existing literature regarding OB-induced behavioral and neurochemical changes, and suggest a possible underlying mechanism that can account for the antidepressant effect of fluoxetine in this model.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Fluoxetina/farmacologia , Hipocampo/citologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Análise de Variância , Anedonia/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Feminino , Preferências Alimentares/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/efeitos dos fármacos , Hipercinese/tratamento farmacológico , Hipercinese/etiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Transtornos do Olfato/complicações , Transtornos do Olfato/etiologia , Bulbo Olfatório/cirurgia , Proteína Oncogênica v-akt/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rosemary, Rosmarinus ofï¬cinalis L., has several therapeutic applications in folk medicine for the treatment of a wide range of diseases, including depression. AIM OF THE STUDY: To evaluate the ability of Rosmarinus ofï¬cinalis hydroalcoholic extract (ROHE), as compared to the positive control fluoxetine, to reverse behavioral (hyperactivity, anhedonic behavior and learning deficit in water maze) and biochemical alterations (serum glucose level and acetylcholinesterase, AChE, activity) induced by an animal model of depression, the olfactory bulbectomy (OB) in mice. MATERIALS AND METHODS: Locomotor and exploratory behavior was assessed in the open-field, novel object and novel cage tests, anhedonic behavior was assessed in the splash test; cognitive deficits were evaluated in the water maze task. For the first set of experiments, ROHE (10-300 mg/kg) or fluoxetine (10mg/kg) was administered once daily (p.o.) for 14 days after OB and the behavioral tests were performed. For the second set of experiments, serum glucose and hippocampal and cerebrocortical AChE activity were determined in OB and SHAM-operated mice treated orally with ROHE (10mg/kg), fluoxetine (10mg/kg) or vehicle. RESULTS: ROHE (10-300 mg/kg), similar to fluoxetine, reversed OB-induced hyperactivity, increased exploratory and anhedonic behavior. OB needed significantly more trials in the training session to acquire the spatial information, but they displayed a similar profile to that of SHAM mice in the test session (24h later), demonstrating a selective deficit in spatial learning, which was not reversed by ROHE or fluoxetine. A reduced serum glucose level and an increased hippocampal AChE activity were observed in bulbectomized mice; only the latter effect was reversed by fluoxetine, while both effects were reversed by ROHE. CONCLUSIONS: ROHE exerted an antidepressant-like effect in bulbectomized mice and was able to abolish AchE alterations and hypoglycemia, but not spatial learning deficit induced by OB. Overall, results suggest the potential of Rosmarinus officinalis for the treatment of depression, validating the traditional use of this plant.
Assuntos
Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Deficiências da Aprendizagem/metabolismo , Aprendizagem/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Rosmarinus , Acetilcolinesterase/metabolismo , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Glicemia/metabolismo , Depressão/complicações , Depressão/metabolismo , Comportamento Exploratório/efeitos dos fármacos , Feminino , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipercinese/tratamento farmacológico , Hipercinese/etiologia , Hipercinese/metabolismo , Hipoglicemia/tratamento farmacológico , Deficiências da Aprendizagem/tratamento farmacológico , Deficiências da Aprendizagem/etiologia , Camundongos , Camundongos Endogâmicos , Bulbo Olfatório/cirurgia , Extratos Vegetais/farmacologiaRESUMO
In this study, we describe three patients who each had an electroclinical overlap of two different epileptic encephalopathies (EE), with onset in a certain age period. Patient 1 had electroclinical features compatible with continuous spikes and waves during slow sleep (CSWSS) syndrome that changed into Lennox-Gastaut syndrome (LGS) (symptomatic, cause porencephalic cyst) at the age of 8.5 years. Patient 2 had LGS which evolved into CSWSS at the age of 6 years (symptomatic, cause polymicrogyria). The third patient had cryptogenic CSWSS syndrome at age the age of 7 years which evolved into LGS at the age of 7.5 years. All three patients could be considered to have two EE: CSWSS syndrome and LGS or to have had overlapping features of these epileptic syndromes.
Assuntos
Encefalopatias/fisiopatologia , Eletroencefalografia , Epilepsia/fisiopatologia , Agressão/psicologia , Encefalopatias/complicações , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/psicologia , Criança , Pré-Escolar , Progressão da Doença , Epilepsia/etiologia , Epilepsia Rolândica/fisiopatologia , Epilepsia Tônico-Clônica/fisiopatologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Hipercinese/etiologia , Hipercinese/fisiopatologia , Deficiência Intelectual/fisiopatologia , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/psicologia , Síndrome de Lennox-Gastaut , Masculino , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/psicologia , Transtornos dos Movimentos/complicações , Transtornos dos Movimentos/psicologia , Convulsões/fisiopatologia , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Espasmos Infantis/fisiopatologiaRESUMO
X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal metabolism, biochemically characterized by deficient beta-oxidation of saturated very long chain fatty acids (VLCFA). The consequent accumulation of these fatty acids in different tissues and in biological fluids is associated with a progressive central and peripheral demyelination, as well as with adrenocortical insufficiency and hypogonadism. Seven variants of this disease have been described, cerebral childhood being the most frequent. The recommended therapy consists of the use of the glyceroltrioleate/glyceroltrierucate mixture known as Lorenzo's Oil (LO), combined with a VLCFA-poor diet, but only in asymptomatic patients will this treatment prevent the progression of the symptomatology. In the present study we evaluated the biochemical course of patients with cerebral childhood (CCER) and asymptomatic clinical forms of X-ALD treated with LO associated with a VLCFA-restricted diet. We observed that hexacosanoic acid plasma concentrations and hexacosanoic/docosanoic ratio were significantly reduced in CCER patients during treatment when compared with diagnosis. Hexacosanoic acid plasma level was significantly reduced when compared with that at diagnosis and achieved the normal levels only in asymptomatic patients under LO treatment. In asymptomatic patients the magnitude of hexacosanoic acid decrease was higher than that of the CCER patients. These results show the good biochemical response of LO treatment in asymptomatic X-ALD patients. It is possible to suppose that this could be correlated with the prevention of the appearance of neurological signals in this group of patients treated with LO.
Assuntos
Adrenoleucodistrofia/sangue , Adrenoleucodistrofia/dietoterapia , Ácidos Erúcicos/uso terapêutico , Ácidos Graxos/sangue , Trioleína/uso terapêutico , Adrenoleucodistrofia/psicologia , Criança , Dieta , Combinação de Medicamentos , Ácidos Graxos/metabolismo , Feminino , Humanos , Hipercinese/etiologia , Hipercinese/psicologia , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/psicologia , Masculino , Convulsões/etiologia , Convulsões/psicologiaRESUMO
INTRODUCTION: Alzheimer's disease (AD) is a degenerative dementia that may disclose different cognitive, behavioral, psychiatric and functional symptoms since onset. These distinct cognitive profiles support the conception of clinical heterogeneity and account for AD's highly variable rate of progression. In spite of strict diagnostic criteria NINCS ADRDA's and DSM IV the clinical certainty is only about 85%. Mayeux define 4 subtypes: a). Benign: mild cognitive and functional impairment without focal signs and late onset behavioral signs, slow progression; b). Myoclonic: usually of presenile onset with severe cognitive deterioration, mutism and early onset myoclonus; c). Extrapyramidal: early onset akineto rigid signs with severe cognitive, behavioral and psychiatric involvement; d). Typical: gradual and progressive cognitive, behavioral and functional impairment. The differentiation of these subtypes will allow us to define discrete patterns of progression, to define prognostic subgroups, and to homogenize them for clinical research and drug trials. DEVELOPMENT: We examined 1000 charts of probable AD patients from the Santojanni Center. We found 42% extrapyramidal, 35% typical, 15% benign and 8% myoclonic. The early onset of parkinsonism and myoclonus predict a rapidly evolving cognitive impairment and a more severe rate of progression with psychiatric disorders and dependency in activities of daily living. (DADL) Patients with low level of education, low cognitive performance at entry as well as those with rapid rate of cognitive deterioration had a faster rate of progression to DADL. CONCLUSION: Delusions, low level of education, extrapyramidal signs and motor hyperactivity but not hallucinations, and anosognosia were the best non cognitive predictors of DADL.
Assuntos
Doença de Alzheimer/classificação , Atividades Cotidianas , Idade de Início , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Doenças dos Gânglios da Base/etiologia , Cerebelo/fisiopatologia , Progressão da Doença , Escolaridade , Lobo Frontal/fisiopatologia , Alucinações/etiologia , Humanos , Hipercinese/etiologia , Transtornos Mentais/etiologia , Mioclonia/etiologia , Exame Neurológico , Transtornos do Olfato/etiologia , Transtornos da Percepção/etiologia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Se define como de gran importancia la actividad de motivación en la relación del odontopediatra con su paciente, se describe una entidad nosológica conocida como déficit atencional e hiperactividad. Las diferentes interpretaciones que a esos niños se les prodiga y las estrategias que se proponen para lograr una adecuada atención odontopediátrica en este especial grupo en los que la comorbilidad de más de una patología dificultan enormemente la terapéutica
Assuntos
Humanos , Masculino , Feminino , Assistência Odontológica para Crianças/métodos , Transtornos do Comportamento Infantil/diagnóstico , Hipercinese/diagnóstico , Motivação , Relações Dentista-Paciente , Hipercinese/epidemiologia , Hipercinese/etiologia , Hipercinese/terapia , Metilfenidato/uso terapêutico , Neurotransmissores/fisiologia , Equipe de Assistência ao PacienteRESUMO
Se define como de gran importancia la actividad de motivación en la relación del odontopediatra con su paciente, se describe una entidad nosológica conocida como déficit atencional e hiperactividad. Las diferentes interpretaciones que a esos niños se les prodiga y las estrategias que se proponen para lograr una adecuada atención odontopediátrica en este especial grupo en los que la comorbilidad de más de una patología dificultan enormemente la terapéutica (AU)
Assuntos
Humanos , Masculino , Feminino , Assistência Odontológica para Crianças/métodos , Motivação , Hipercinese/diagnóstico , Transtornos do Comportamento Infantil/diagnóstico , Relações Dentista-Paciente , Hipercinese/etiologia , Hipercinese/epidemiologia , Hipercinese/terapia , Equipe de Assistência ao Paciente , Metilfenidato/uso terapêutico , Neurotransmissores/fisiologiaRESUMO
A group of 22 hyperactive children from 7 to 12 years of age was selected among 38 out-patients registered at Hospital do Servidor Público de São Paulo (Civil Servant Hospital of the State of São Paulo). Their psychiatric evaluation was negative, the neurological examination showed "psychomotor syndrome", and psychological evaluation revealed disorders related with Ego maturation in all cases. Although all children were referred to psychotherapy, only thirteen underwent individual sessions once a week for an uninterrupted period of up to one year. Neither diets nor medicines were prescribed. After six months and one year of treatment, the children were reevaluated. They showed improved school performance, reduced hyperactivity, and better internal psychic organization. These results are considered as undeniable evidence of the psychodynamic origin of hyperactivity syndrome in children, when no definite neurologic or psychiatric diseases are demonstrated.
Assuntos
Hipercinese/etiologia , Atenção , Teste de Bender-Gestalt , Criança , Ego , Feminino , Humanos , Hipercinese/psicologia , Hipercinese/terapia , Masculino , Anamnese , Estudos Prospectivos , Agitação Psicomotora , PsicoterapiaRESUMO
A group of 22 hyperactive children from 7 to 12 years of age was selected among 38 out-patients registered at Hospital do Servidor Público de Sao Paulo (Civil Servant Hospital of the State of Sao Paulo). Their psychiatric evaluation was negative, the neurological examination showed "psychomotor syndrome", and psychological evaluation revealed disorders related with Ego maturation in all cases. Although all children were referred to psychotherapy, only thirteen underwent individual sessions once a week for an uninterrupted period of up to one year. Neither diets nor medicines were prescribed. After six months and one year of treatment, the children were reevaluated. They showed improved school performance, reduced hyperactivity, and better internal psychic organization. These results are considered as undeniable evidence of the psychodynamic origin of hyperactivity syndrome in children, when no definite neurologic or psychiatric diseases are demonstrated.
Assuntos
Humanos , Masculino , Feminino , Criança , Hipercinese/etiologia , Atenção , Teste de Bender-Gestalt , Ego , Hipercinese/psicologia , Hipercinese/terapia , Anamnese , Estudos Prospectivos , Agitação Psicomotora , PsicoterapiaRESUMO
We studied the role of oligoantigenic diets in 63 children with epilepsy; 45 children had epilepsy with migraine, hyperkinetic behavior, or both, and 18 had epilepsy alone. Of the 45 children who had epilepsy with recurrent headaches, abdominal symptoms, or hyperkinetic behavior, 25 ceased to have seizures and 11 had fewer seizures during diet therapy. Headaches, abdominal pains, and hyperkinetic behavior ceased in all those whose seizures ceased, and in some of those whose seizures did not cease. Foods provoking symptoms were identified by systematic reintroduction of foods, one by one; symptoms recurred with 42 foods, and seizures recurred with 31; most children reacted to several foods. Of 24 children with generalized epilepsy, 18 recovered or improved (including 4 of 7 with myoclonic seizures and all with petit mal), as did 18 of 21 children with partial epilepsy. In double-blind, placebo-controlled provocation studies, symptoms recurred in 15 of 16 children, including seizures in eight; none recurred when placebo was given. Eighteen other children, who had epilepsy alone, were similarly treated with an oligoantigenic diet; none improved.
Assuntos
Epilepsia/dietoterapia , Hipersensibilidade Alimentar/complicações , Transtornos de Enxaqueca/dietoterapia , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Eletroencefalografia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Seguimentos , Humanos , Hipercinese/etiologia , Transtornos de Enxaqueca/etiologia , Recidiva , Testes CutâneosAssuntos
Doença de Huntington/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Anfetamina/administração & dosagem , Animais , Antipsicóticos/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/efeitos adversos , Discinesia Induzida por Medicamentos/fisiopatologia , Humanos , Hipercinese/etiologia , Modelos Neurológicos , Neurotransmissores/fisiologia , Doença de Parkinson/fisiopatologia , Fisostigmina/administração & dosagem , Ratos , Ácido gama-Aminobutírico/fisiologiaRESUMO
An attempt was made to indicate the neuropharmalogical relationship between Parkinson's disease, Huntington's chorea, tardive dyskinesia and Attentional Deficit Disorder. In the case of the latter, an experimental model has been prersented indicating cholinergic dysfunction in the nigro-striatal pathway. Postulates are proposed which will enable us to understand the many factors responsible for these clinical states. (AU)
Assuntos
Humanos , Animais , Ratos , Doença de Huntington/fisiopatologia , Transtornos Motores/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Anfetamina/administração & dosagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Cérebro/efeitos dos fármacos , Inibidores da Colinesterase/efeitos adversos , Discinesia Induzida por Medicamentos/fisiopatologia , Ácido gama-Aminobutírico/fisiologia , Hipercinese/etiologia , Modelos Neurológicos , Neurotransmissores/fisiologia , Doença de Parkinson/fisiopatologia , Fisostigmina/administração & dosagem , Jamaica , Antipsicóticos/efeitos adversosRESUMO
The neurologic course of congenital rubella syndrome was traced in 29 nonretarded children to 9 to 12 years. During the first two years, manifestations involved abnormal tone and reflexes (69%), motor delays (66%), feeding difficulties (48%), and abnormal clinical behavior (45%). Hearing loss was documented in 76%. From three to seven years, poor balance, motor incoordination (69%), and behavioral disturbances (66%) predominated. Hearing losses increased to 86%. Currently, at 9 to 12 years, 25 have residua which include learning deficits (52%), behavioral disturbances (48%), poor balance (61%), muscle weakness (54%), and deficits in tactile perception (41%). Two additional children now have hearing loss. The encephalitic manifestations of congenital rubella syndrome are diverse. Overriding problems differ at each phase of childhood. Current deficits influence progress in educational and home environments. For these children, adequate intelligence alone does not guarantee academic success.
Assuntos
Encefalite/congênito , Rubéola (Sarampo Alemão)/congênito , Peso ao Nascer , Criança , Deficiências do Desenvolvimento/etiologia , Eletroencefalografia , Encefalite/complicações , Feminino , Perda Auditiva Neurossensorial/etiologia , Humanos , Hipercinese/etiologia , Lactente , Recém-Nascido , Inteligência , Deficiências da Aprendizagem/etiologia , Masculino , Doenças Musculares/etiologia , Postura , Rubéola (Sarampo Alemão)/complicações , Transtornos da Visão/etiologiaRESUMO
The cardinal features of the hyperkinetic child syndrome is excessive non-goal directed motor overactivity and impulsivity. Although hyperactive children constitute a small part of their age group, 4 percent - Steward et al 1966, their effects on peers and demands on teachers and parents are far out of proportion to their number. In addition, the linkage between hyperkinesia and adult psychopathology (like-emotional immaturity, inability to attain goals, feelings of hopelessness and poor self image) has been inferred from longitudinal, retrospective and family studies (Arnold et al 1972, Huessy 1974, Robins 1966). The present drugs of choice for the treatment of hyperkinesia (central nervous system stimulants like methylphenidate and d-amphetamine), have serious side effects and long periods of administration are known to cause psychosis (Laufer and Denhoff 1957). In the light of the above problems, fundamental research aimed at elucidating the biochemical determinants of hyperkinesia would be very useful, as this might result in better pharmaco-therapy for the syndrome. However, caution should be excercised in extrapolating results from animal to man. Since a functional interrelationship exists between dopaminergic and cholinergic systems (Sethy and Van Woert 1974), in the extrapyramidal system (this is important for the control of motor activity in man and other mammals), it was therefore hypothesized that motor hyperactivity could be due to a cholinergic inbalance in the brain. Rats' motor activity would seem a reasonable model for this study, as the main symptom of this syndrome is motor hyperactivity. Female rats (mean body weight 200 ñ 5G) were used for this study. Motor activity was measured with jiggle platforms which monitor the gross motor activity of the test animals as opposed to photoelectric activity cages which only measure animals locomotion. All drugs used for this study were injected intraperitoneally at a volume of 0.1ml, and the testing period for each rat was 60-min. Physostigmine at dose levels (0.01 - 0.18mg/kg) significantly increased rats motor activity as compared to saline controls. This increase in motor activity was also obtained when physostigmine at 0.05mg/kg was injected daily for four days. Atropine sulphate (5 and 10 mg/kg) attentuated the physostigmine induced increase in motor activity. However, the physostigmine induced excitation was potentiated by d-amphetamine at 1, 2 and 4mg/kg. These effects occurred whether physostigmine was injected before or after atropine and d-amphetamine. The effect of physostigmine on motor activity is central as neostigmine did not induce any stimulation of rats' motor activity. In addition reserpine, phenobarbitone, haloperidol and practocol (a beta-adrenergic blocking drug), attentuated the physostigmine-induced increase in motor activity, while phentolamine and tranylcypromine (MAO Inhibitor) did not affect the physostigmine-induced excitation. These results are discussed in conjunction with the findings of other workers and is concluded that: (i) increasing the acetylcholine level of the rats brain with an anticholinesterase (physostigmine) induces motor hyperactivity: (ii) anticholinergics and neuroleptics are capable of attenuating this physostigmine-induced motor hyperactivity. (iii) the fact that d-amphetamine potentiated the physostigmine-induced motor hyperactivity may exlain the observation that following d-amphetamine or methylphenidate treatment, some hyperkinetic children (30 percent) manifest a worsening of their symptoms. (Satterfield et al 1972). If in some subtypes of hyperkinetics, a cholinergic dysfunction is present, then it follows on the basis of the present study that d-amphetamine will excercebate their condition, while anticholinergics might be useful therapy (AU)