RESUMEN
Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.
Asunto(s)
Bronquiectasia/genética , Pulmón/diagnóstico por imagen , Mutación Missense , Deficiencia de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Bronquiectasia/sangre , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/fisiopatología , Monóxido de Carbono , Femenino , Volumen Espiratorio Forzado , Genotipo , Heterocigoto , Humanos , Pulmón/fisiopatología , Persona de Mediana Edad , Capacidad de Difusión Pulmonar , Volumen Residual , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos X , Capacidad Pulmonar Total , Capacidad Vital , alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/fisiopatologíaRESUMEN
CONTEXT: Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, encoded by CYP21A2 gene, is an autosomal recessive disorder. The CYP21A2 gene, localized in a genetic unit defined RCCX module, is considered one of the most polymorphic of human genes. OBJECTIVES: We considered new evidences about the presence of a RCCX trimodular haplotype with a CYP21A2-like gene to explain the lack of a genotype-phenotype correlation in individuals of two different families. DESIGN AND METHODS: To verify gene duplication we used Multiplex Ligation Probe-Dependent Amplifications (MLPA) and to confirm the presence of a CYP21A2-like gene downstream TNXA gene we used previously described amplification and restriction strategy followed by the sequencing of the CYP21A2 gene downstream TNXB gene. RESULTS: The amplification strategy and restriction analysis of CYP21A1P/CYP21A2-TNXA PCR product in association with MLPA assay and sequencing of CYP21A2 gene downstream TNXB were able to identify the presence of the CYP21A2-like gene in healthy subjects of the two families, wherein the direct sequencing of CYP21A2 gene showed genotypes correlated to pathological phenotypes. CONCLUSIONS: The strategy suggested is useful to facilitate molecular testing in CAH patients, considering the new evidence about possible different haplotypes.
Asunto(s)
Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Genotipo , Fenotipo , Esteroide 21-Hidroxilasa/genética , Niño , Femenino , Humanos , Persona de Mediana Edad , LinajeRESUMEN
Breast cancer is the most common cancer among women in Western countries (130,000 cases per year in Europe) and accounts for 20-25% of all malignancies in European women. In the past few years medical journals have focused greater attention on the quality and quantity of information provided to consumers; there is a general consensus amongst physicians on the importance of having better informed consumers. This change in attitude is influencing greatly the physician-patient relationship and political decisions. Breast cancer associations, like the National Breast Cancer Coalition in the USA or EUROPA DONNA, the European Breast Cancer Coalition in Europe, have pushed for involvement in the discussion of any phase of illness, and have a particular interest in preventive medicine. The identification of high-risk women by genetic testing for BRCA1 and BRCA2 mutations is largely debated, in particular regarding patient counseling, and psychosocial and legislative support. This article reports the different points of view raised by women's movements, so that useful suggestions may be provided to improve breast cancer prevention modalities.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Pruebas Genéticas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Europa (Continente) , Femenino , Humanos , Italia , MutaciónRESUMEN
BACKGROUND: A retrospective study of 444 patients undergoing urgent and emergent coronary artery bypass grafting for acute coronary insufficiency was performed to identify the risk factors for hospital death specifically associated with the clinical severity of the acute coronary insufficiency syndrome. METHODS: The patients were divided into three groups-urgent, emergent A, and emergent B-on the basis of the evolution of the clinical pattern of the acute coronary insufficiency syndrome on full medical treatment. The three categories were defined as follows: urgent (257 patients), surgical revascularization could be delayed for 24 to 36 hours after surgical consultation because of adequate control of ischemia; emergent A (127 patients), prompt myocardial revascularization was required because medical treatment achieved only transient regression of an unrelenting ischemic pattern; and emergent B (60 patients), prompt myocardial revascularization was required because the acute coronary insufficiency was entirely refractory to medical treatment. RESULTS: Mortality rates were 7.4% for the urgent group, 13.4% for the emergent A group, and 31.7% for the emergent B group. Multivariate analysis identified the following as risk factors for hospital mortality: ejection fraction (p = 0.023) and aortic cross-clamp time (p = 0.10) for the urgent group; aortic cross-clamp time (p = 0.017), ejection fraction (p = 0.03), and nonuse of blood cardioplegia (p = 0.04) for the emergent A group; and cardiogenic shock (p = 0.00), preoperative ischemic interval (p = 0.00), aortic cross-clamp time (p = 0.018), and nonuse of blood cardioplegia (p = 0.012) for the emergent B group. CONCLUSIONS: A more exact definition of patient risk can be achieved when predictive outcome models are constructed using the risk factors specifically related to each level of clinical severity of the ischemic syndrome.
Asunto(s)
Puente de Arteria Coronaria/mortalidad , Mortalidad Hospitalaria , Isquemia Miocárdica/cirugía , Sangre , Soluciones Cardiopléjicas/uso terapéutico , Puente Cardiopulmonar , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/complicaciones , Trombosis Coronaria/complicaciones , Urgencias Médicas , Femenino , Predicción , Paro Cardíaco Inducido , Humanos , Complicaciones Intraoperatorias , Italia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/fisiopatología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Síndrome , Terapia Trombolítica , Factores de Tiempo , Resultado del TratamientoRESUMEN
We report a case of a 63-year-old woman who presented with pseudoaneurysm of the free wall of the left ventricle secondary to myocardial infarction, in the presence of angiographically normal major coronary arteries. This is the only such case we know of, in which the patient underwent successful surgical correction. At last follow-up, the patient was in good condition with no evidence of cardiac disease, at 9 years after surgery.
Asunto(s)
Aneurisma Falso/etiología , Aneurisma Cardíaco/etiología , Rotura Cardíaca Posinfarto/cirugía , Aneurisma Falso/diagnóstico , Aneurisma Falso/cirugía , Angiografía Coronaria , Electrocardiografía , Femenino , Estudios de Seguimiento , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/cirugía , Rotura Cardíaca Posinfarto/diagnóstico , Ventrículos Cardíacos , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
OBJECTIVES: A retrospective analysis of 444 patients (Pts) with acute coronary insufficiency (A.C.I.) submitted to coronary artery bypass grafting between January '85 and December '92 was performed in order to identify incremental risk factors associated with perioperative mortality and to evaluate whether prediction of mortality can be accomplished utilizing risk models specifically linked to the severity of myocardial ischemia. METHODS: Based on clinical and ECGraphic standpoints three different groups were identified: urgent group, comprehensive of 257 Pts. in whom, because of full medically controlled ischemia, myocardial revascularization could be delayed until to 24-48 hours. Emergency-A group, comprehensive of 127 Pts with recurrent ischemia despite medical therapy, but with no signs of coronary insufficiency at the time of institution of cardiopulmonary bypass (CPB). Emergency-B group, comprehensive of 60 Pts operated on after a mean preoperative ischemic interval of 3.9 +/- 2.4 hours who presented unrelenting signs of ischemia, either persisting since the inception of the clinical picture or lasting for over 30 minutes at the time of institution of CPB; among those, 27 Pts were in cardiogenic shock. RESULTS: Mortality rate in the three groups was respectively: 7.4%, 13.4%, 31.7%. Multivariate analysis identified the following risk factors of in-hospital mortality: urgent group: aortic cross-clamping time (A.C.C.T.) (p = 0.10) and ejection fraction (E.F.) (p = 0.023). Emergency-A group: A.C.C.T. (p = 0.017), E.F. (p = 0.023) and non-use of blood cardioplegia (B.C.) (p = 0.04). Emergency-B group: cardiogenic shock (p = 0.00), preoperative ischemic interval > 6 hours (p = 0.00), A.C.C.T. (p = 0.018) and non-use of B.C. (p = 0.012). CONCLUSIONS: A useful stratification of Pts with A.C.I. in three different groups, each with its own risk model, can be obtained by means of clinical-ECGraphic criteria alone. Different prognostic weights can be attributed to the variables A.C.C.T., E.F. and non-use of B.C. depending on clinical status. A significant reduction of mortality rate in Pts with cardiogenic shock can be achieved by the utilization of individually-tailored surgical management.
Asunto(s)
Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/cirugía , Revascularización Miocárdica , Enfermedad Aguda , Distribución de Chi-Cuadrado , Enfermedad Coronaria/diagnóstico , Electrocardiografía , Urgencias Médicas , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Italia/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica/métodos , Revascularización Miocárdica/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The effects of phencyclidine (PCP) on the threshold and intensity of caffeine-induced convulsions in rats were examined. There was a dose-dependent effect of PCP on convulsion intensity with significant reduction in intensity at 4.0 and 8.0 mg/kg PCP. At 16.0 mg/kg PCP, convulsant intensity was reduced in 50% of subjects but potentiated to the point of death in the remaining 50%. PCP had no significant effect on threshold for caffeine-induced convulsions. These results suggest that PCP antagonizes caffeine-induced convulsions and further suggests that the mechanisms involved in onset of caffeine-induced convulsions and the decrease of convulsion intensity are pharmacologically dissociable.
Asunto(s)
Cafeína , Fenciclidina/farmacología , Convulsiones/fisiopatología , Animales , Cafeína/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Fenciclidina/administración & dosificación , Ratas , Ratas Endogámicas , Convulsiones/inducido químicamenteRESUMEN
The pharmacology and structure-activity relationship of phencyclidine (PCP)-like drugs (phencyclinoids) were studied using electroencephalographic (EEG), behavioral and receptor binding techniques. The effects of PCP, 1-phenylcyclohexylamine HCl, N-methyl-1-phenycyclohexylamine HCl, N-ethyl-1-phenylcyclohexylamine HCl, N-(s-butyl)-1-phenylcyclohexylamine HCL, 1-(1-phenylcyclo-hexyl)-pyrrolidine HCl, 1-[1-(2-thienyl)cyclohexyl] piperidine HCl, 1-[1-(2-thienyl)cyclohexyl]-pyrrolidine HCl, ketamine and (+/-)-SKF 10047 were evaluated on the direct EEG and EEG spectra after acute i.v. injections (0.1-17.8 mg/kg). Similarities and differences were noted in the EEG dose-response curves. At lower doses of PCP and its analogs, low-amplitude theta waves predominated; however, at higher doses, high-amplitude, lower-frequency waves predominated. Qualitatively, the N-piperidine derivatives were similar to PCP and differed primarily in potency. The benzomorphan (+/-)-SKF 10047 produced only theta activity at doses up to 12.8 mg/kg. These EEG effects occurred in conjunction with overt behaviors including locomotion, stereotypy and ataxia, concurrently assessed via observer-based rating scales. A strong correlation (r = 0.98) was obtained between the EEG and behavioral effects and the IC50 values from [3H]PCP displacement experiments using crude rat brain homogenates.
Asunto(s)
Conducta Animal/efectos de los fármacos , Electroencefalografía , Fenciclidina/análogos & derivados , Fenciclidina/farmacología , Receptores de Neurotransmisores/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Femenino , Inyecciones Intravenosas , Fenciclidina/metabolismo , Ratas , Ratas Endogámicas , Receptores de Neurotransmisores/metabolismo , Receptores de Fenciclidina , TritioRESUMEN
It has been suggested that dopamine (DA)-containing neurons within the medial prefrontal cortex subserve a role in the positive reinforcing effects of psychomotor stimulants. Injections of 6-hydroxydopamine (6-OHDA) into this region, which destroyed a major portion of the DA innervation, but maintained the integrity of noradrenergic and serotonergic neurons, failed to alter either the acquisition or maintenance of the intravenous self-administration of d-amphetamine in rats. Compared to vehicle-injected controls (sham lesions), the animals treated with 6-OHDA acquired the drug-abuse behaviour and maintained comparable, stable rates of self-injection. The lesions increased concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens septi but not in the striatum. The increased synthesis of DA in the nucleus accumbens septi [demonstrated by increased accumulation of dihydroxyphenylalanine (DOPA)] was abolished by the intravenous administration of d-amphetamine, in patterns mimicking those of animals trained in self-administration.
Asunto(s)
Anfetamina/farmacología , Encéfalo/metabolismo , Dopamina/biosíntesis , Dopamina/fisiología , Lóbulo Frontal/fisiología , Neuronas/fisiología , Animales , Lóbulo Frontal/citología , Lóbulo Frontal/patología , Hidroxidopaminas/farmacología , Masculino , Neuronas/patología , Oxidopamina , Ratas , Ratas Endogámicas , AutoadministraciónRESUMEN
The effects of chronic phencyclidine (PCP) or ketamine (KET) on their respective acute behavioral and anticonvulsant actions were investigated. Female rats were treated for 15 days with twice daily i.p. injections of saline, 20 mg/kg PCP or 40 mg/kg KET. Subjects treated chronically with PCP were challenged with either 10 mg/kg or 20 mg/kg i.p. PCP, while subjects treated chronically with KET were challenged with 40 mg/kg i.p. KET only. Neither chronic drug treatment induced tolerance to the acute anticonvulsant effect, nor to hyperlocomotion and stereotypy as measured by automated activity monitors. However, evidence of tolerance to the stereotypy induced by acute KET was obtained when an observer-based rating scale was employed. In addition, tolerance occurred to the ataxia induced by KET and the 10 mg/kg, but not 20 mg/kg, dose of PCP. Thus, tolerance occurs to some of the acute behavioral effects of PCP and KET while the anticonvulsant action of these compounds remains unaffected.
Asunto(s)
Anticonvulsivantes , Ketamina/farmacología , Actividad Motora/efectos de los fármacos , Fenciclidina/farmacología , Animales , Tolerancia a Medicamentos , Electrochoque , Femenino , Ratas , Ratas Endogámicas , Conducta Estereotipada/efectos de los fármacosRESUMEN
Previously, it had been shown that lesions of cerebral 5-hydroxytryptamine (5-HT)-containing neurons and injections of drugs affecting 5-HT synthesis or receptor mediated function would alter amphetamine self-administration in the rat. The present study sought to ascertain whether diets enriched in L-tryptophan (L-TRY), the amino acid precursor to 5-HT, would: elevate cerebral 5-HT concentrations and affect amphetamine self-administration behavior. Diets containing 2.0 and 4.0% L-TRY increased cerebral 5-HT concentrations above those of rats on normal rat chow (0.26% L-TRY). The 4.0% diet elevated brain 5-HT to the same degree in rats exposed to the diet for 1, 2 or 3 days. When normal diets were restored, brain 5-HT concentrations rapidly returned to normal. Animals trained to self-administer d-amphetamine, when given access to the L-TRY enriched diets, significantly reduced their daily amphetamine self-injection during exposure periods. When normal rat chow was restored a delay in recovery to pre-diet amphetamine self-administration was observed: 1 day with the 2.0% L-TRY diet and 2 days with the 4.0% L-TRY diet. The 4.0% L-TRY diet failed to alter saline-frustration responding indicating the diet did not produce decrements in motor performance. When animals were placed on the 4.0% L-TRY diet and allowed access to amphetamine for 1 day then exposed to saline, a profound decrease in saline-frustration responding was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Química Encefálica/efectos de los fármacos , Dextroanfetamina/administración & dosificación , Serotonina/metabolismo , Triptófano/farmacología , Animales , Aminas Biogénicas/metabolismo , Condicionamiento Operante , Dieta , Ácido Hidroxiindolacético/metabolismo , Masculino , Ratas , Ratas Endogámicas , Refuerzo en Psicología , AutoadministraciónRESUMEN
Dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in brain were examined in the striatum and nucleus accumbens septi after the administration of amphetamine by two different methods. A computer-controlled device was constructed to deliver intravenous injections of amphetamine in patterns mimicking those of animals in a self-administration paradigm, i.e. a total of 65 injections of 0.125 mg/kg/injection over 8 hr [total; 8.13 mg/kg (22.05 mumoles/kg)]. The second method was the intraperitoneal injection of 8.13 mg/kg as a single bolus. Control animals were intravenously or intraperitoneally administered saline. The effects of the two injection methods on the concentrations of DA and DOPAC were quite distinct at early times. This may in part be due to differences in the peak concentrations of amphetamine in brain achieved by the two regimens. Differences still persisted 48 hr after injection, particularly in the striatum. Increased levels of DA and DOPAC were observed at this time after the computer-controlled injections, while significantly decreased DA in the striatum is found after intraperitoneal bolus injections. These data strongly suggest that the method of administration of amphetamine can substantially alter the effects and possible toxicity of the drug on dopaminergic systems.
Asunto(s)
Anfetamina/administración & dosificación , Dopamina , Neuronas/efectos de los fármacos , Ácido 3,4-Dihidroxifenilacético/análisis , Animales , Encéfalo/citología , Química Encefálica , Computadores , Dextroanfetamina/administración & dosificación , Dopamina/análisis , Masculino , Ratas , Ratas Endogámicas , AutoadministraciónRESUMEN
The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Anticonvulsivantes/farmacología , Convulsivantes/farmacología , Fenciclidina/farmacología , Animales , Fenómenos Químicos , Química , Relación Dosis-Respuesta a Droga , Femenino , Ketamina/farmacología , Fenazocina/análogos & derivados , Fenazocina/farmacología , Fenciclidina/análogos & derivados , Ratas , Ratas Endogámicas , Relación Estructura-ActividadAsunto(s)
Encéfalo/fisiología , Actividad Motora/efectos de los fármacos , Fenciclidina/farmacología , Receptores de Neurotransmisores/metabolismo , Conducta Estereotipada/efectos de los fármacos , Analgésicos , Animales , Anticonvulsivantes , Ataxia/fisiopatología , Encéfalo/efectos de los fármacos , Electroencefalografía , Femenino , Fenciclidina/análogos & derivados , Fenciclidina/metabolismo , Postura , Ratas , Ratas Endogámicas , Receptores de Fenciclidina , Reflejo/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
The present experiments investigated the role of ACTH fragments in d-amphetamine self-administration in rats. Presession injections of 20 or 40 ug/80 ul ACTH1-24 (but not 10 ug/80 ul ACTH1-24 nor any dose of ACTH4-10) significantly reduced rates of d-amphetamine self-infusion for 2 days. Neurochemical experiments revealed that ACTH1-24, followed 24hr later by haloperidol, attenuated haloperidol-induced increases in HVA and DOPAC in both the caudate and nucleus accumbens. It was tentatively concluded that the corticosteroid mediated neuromodulatory action of ACTH1-24 on dopaminergic neurons might increase the rewarding quality of d-amphetamine, thus rendering control levels of self-infusion superfluous.
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Encéfalo/fisiología , Condicionamiento Operante/efectos de los fármacos , Cosintropina/farmacología , Dextroanfetamina/administración & dosificación , Dopamina/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Apomorfina/farmacología , Encéfalo/efectos de los fármacos , Núcleo Caudado/metabolismo , Dextroanfetamina/farmacología , Relación Dosis-Respuesta a Droga , Haloperidol/farmacología , Ácido Homovanílico/metabolismo , Masculino , Núcleo Accumbens/metabolismo , Ratas , Ratas Endogámicas , AutoestimulaciónRESUMEN
Experiments aimed at determining the neural basis of reward have previously focused on the role of neurotransmitters and have only recently begun to investigate the role of peptides. The present experiment investigated the effect of ACTH1-24 on d-amphetamine self-administration in rats. Animals were trained daily (8 hour sessions) to press a lever which activated a system that administered 0.125 mg/kg of intravenous amphetamine. After achievement of a stable self-injection frequency, subjects were injected SC with 10, 20 or 40 micrograms/80 microliters ACTH1-24 immediately prior to placement in the apparatus. The 20 micrograms and 40 micrograms doses of the peptide fragment induced a statistically significant attenuation of d-amphetamine self-injection which lasted for 2 days. Control rates of responding were achieved by 5 to 10 days after the peptide treatment. An experiment was conducted to evaluate possible neuromodulatory effects of the peptide fragment. Twenty-four hr after ACTH1-24, HVA was elevated in the caudate. When both apomorphine and ACTH1-24 were administered, the combination lowered HVA in the caudate to a greater degree than apomorphine alone. The peptide fragment, when combined with haloperidol, attenuated the haloperidol-induced increases of DOPAC and HVA in both the caudate and nucleus accumbens. It was tentatively concluded that the neuromodulatory action of ACTH1-24 on dopaminergic neurons may result in an increase in the rewarding quality of d-amphetamine, thus rendering control level self-infusions superfluous.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Encéfalo/metabolismo , Cosintropina/farmacología , Dextroanfetamina/administración & dosificación , Dopamina/metabolismo , Autoestimulación/efectos de los fármacos , Animales , Encéfalo/efectos de los fármacos , Ácido Homovanílico/metabolismo , Cinética , Masculino , Especificidad de Órganos , Ratas , Ratas Endogámicas , AutoadministraciónRESUMEN
Animals in which 5,7-dihydroxytryptamine (5,7-DHT) was bilaterally injected into the median forebrain bundle (MFB) and sham lesioned animals were allowed access to an apparatus which delivered, upon lever pressing, intravenous D-amphetamine injections. MFB lesioned rats achieved stable self-injections patterns and self-administered more drug per test session than controls. A number of agents known to either directly or indirectly affect 5-hydroxytryptamine (5-HT) receptor function were administered prior to D-amphetamine access. The responses to these pretreatments in lesioned vs non-lesioned rats were markedly different. Pretreatment with L-tryptophan reduced the number of D-amphetamine self-injections in sham lesioned rats but had no effect in MFB lesioned animals. Fluoxetine pretreatment, likewise, reduced responding in non-lesioned rats and had no observable effect in lesioned animals. Quipazine markedly reduced self-injection in control rats but was not evaluated in the lesioned group. The putative 5-HT antagonists utilized, cyproheptadine and methysergide, unpredictably reduced self-injection frequency of non-lesioned animals in a dose related manner. When MFB lesioned animals were pretreated with cyproheptadine, rapid bursts of lever pressing were observed and 3 of 6 animals thus treated died as a result (presumably amphetamine overdose). In the remaining animals, methysergide produced a similar marked increase in self-injection rate. While these data may suggest that, in some instances, non-serotonergic mechanisms are involved, for the most part it would appear that 5-HT containing neurons are of major import in some aspect of D-amphetamine self-administration.
Asunto(s)
Dextroanfetamina , Haz Prosencefálico Medial/fisiopatología , Vías Nerviosas/fisiopatología , Serotonina/fisiología , Trastornos Relacionados con Sustancias/fisiopatología , 5,7-Dihidroxitriptamina/farmacología , Animales , Ciproheptadina/farmacología , Fluoxetina/farmacología , Humanos , Masculino , Metisergida/farmacología , Quipazina/farmacología , Ratas , Ratas Endogámicas , Triptófano/farmacologíaRESUMEN
Increases and decreases in the concentration or activity of vasopressin (VP) in mice result in facilitations and deficits in avoidance performance, respectively. An experiment was conducted to test the hypothesis that elevations in the central nervous system concentration of VP result from doses of d-amphetamine, strychnine sulfate and physostigmine known to induce facilitations of avoidance performance. An immunohistofluorescent technique was used to determine whether performance-facilitating doses of the three drugs elevated VP levels in a number of brain structures. A performance-facilitating dose of each of the three drugs was found to increase VP-like immunoreactivity in the dorsal raphe and lateral septum, but not in the substantia nigra, dentate gyrus or central amygdaloid nucleus.