RESUMEN
When compared to young Fisher 344 rats, aged Fisher 344 rats were impaired in their acquisition of the water maze task as indicated by longer escape latencies and distances to find a hidden platform. In a free swim trial which was performed after the training period, young rats had a better spatial bias, since they spent more time swimming in the previous training quadrant. Tacrine 3 mg/kg, an anticholinesterase, and selegiline 0.25 mg/kg, a MAO-B inhibitor, partially reversed the acquisition deficit in aged rats when administered on their own, and drug-treated aged rats swam more in the previous training quadrant than vehicle-treated aged rats during the free swim trial. Aged rats also swam slower than young rats. Tacrine, but not selegiline, increased swimming speed in aged rats. Taken as a whole, these data support the proposal that tacrine may be effective at alleviating age-related learning impairment and confirm the role of cholinergic dysfunction in the spatial learning deficit in aged rats.
Asunto(s)
Envejecimiento/psicología , Inhibidores de la Colinesterasa/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Inhibidores de la Monoaminooxidasa/farmacología , Selegilina/farmacología , Tacrina/farmacología , Animales , Evaluación Preclínica de Medicamentos , Reacción de Fuga/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas F344 , Tiempo de Reacción/efectos de los fármacosRESUMEN
Twenty-five (96%) of 26 patients with histologically verified moderate to severe Alzheimer's disease had abnormal electroencephalograms. The patients with the slowest (5-6 Hz) dominant occipital rhythms had significantly lower choline acetyltransferase activity in the post mortem frontal cortex than the patients with highest rhythm (8-9 Hz) (analysis of covariance adjusted for the neuropsychological test score). Concentrations of dopamine, noradrenaline or serotonin in the frontal cortex did not differ in the patient groups with the slowest and highest rhythms. Neither did scores of senile plaques or neurofibrillary tangles differ between these groups. In Alzheimer patients, the frequency of the dominant occipital rhythm correlated with the total score of the neuropsychological test (r = 0.58, P less than 0.01) and with the subscales of praxic functions and expressive speech, memory and general reasoning. The results suggest that the cholinergic deficit may contribute to the slowing of the electroencephalogram found in patients with Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Colina O-Acetiltransferasa/metabolismo , Electroencefalografía , Lóbulo Frontal/fisiopatología , Anciano , Enfermedad de Alzheimer/patología , Autopsia , Femenino , Lóbulo Frontal/enzimología , Lóbulo Frontal/patología , Humanos , Masculino , Ovillos Neurofibrilares/ultraestructura , Valores de ReferenciaRESUMEN
Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG.
Asunto(s)
Aminocaproatos/farmacología , Anticonvulsivantes/farmacología , Electroencefalografía/efectos de los fármacos , Aminocaproatos/administración & dosificación , Animales , Anticonvulsivantes/administración & dosificación , Ritmo Delta/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/fisiología , Inyecciones Intraperitoneales , Masculino , Lóbulo Occipital/efectos de los fármacos , Lóbulo Occipital/fisiología , Ratas , Ritmo Teta/efectos de los fármacos , Vigabatrin , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
Previous studies have shown that a somatostatin-depleting drug, cysteamine (CYS), suppresses kindled seizures. However, no data is available concerning the levels of somatostatin-like immunoreactivity (SLI) in the kindled rat brain after CYS administration. In the present study, we used radioimmunoassay to measure SLI in the frontal cortex, amygdala + piriform cortex, hippocampus, striatum and hypothalamus: 1) in control rats, 2) in amygdala-kindled rats decapitated 14 days after the last stimulus, and 3) in amygdala-kindled rats decapitated 14 days after the last stimulus but treated either 11 days or 4) 4 hours before decapitation with CYS (100 mg/kg, subcutaneously). The results showed that, compared to controls, in kindled rats SLI was elevated both in the ipsi lateral (28%, p = 0.0372) and contralateral (17%, p = 0.0078) frontal cortex. Compared to kindled rats, CYS given 4 hours before decapitation decreased SLI in the frontal cortex (to 71%, p = 0.0066) and hippocampus (to 72%, p = 0.0027), but compared to the controls, only in the hippocampus. In rats given CYS 11 days before decapitation, SLI did not differ from either the controls or from the kindled rats. In conclusion, the somatostatinergic system is affected in amygdala-kindling; but the relationship of anatomical localization and the magnitude of CYS-induced decrease of SLI to elevated seizure threshold needs to be studied further.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Encéfalo/metabolismo , Cisteamina/farmacología , Péptidos/metabolismo , Somatostatina/metabolismo , Amígdala del Cerebelo/metabolismo , Animales , Cuerpo Estriado/metabolismo , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Hipotálamo/metabolismo , Excitación Neurológica/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas , Convulsiones , Factores de TiempoRESUMEN
beta-Endorphin-like immunoreactivity (beta-EP-LI) in cerebrospinal fluid (CSF) was measured in 42 patients with Alzheimer's disease (AD), 36 patients with Parkinson's disease (PD), and 35 controls. Values for patients with Alzheimer's disease (10.9 +/- 2.8 pmol/l) seemed to be lower than those for controls (12.9 +/- 2.5 pmol/l) (P less than 0.05). In addition, the severely demented patients had lower values than the moderately demented (P less than 0.01). In patients with Parkinson's disease no significant difference in beta-EP-LI values was observed compared to the controls. The data suggest, that processing of pro-opiomelanocortin, precursor of beta-endorphin, and the mechanism of cognitive impairment may differ in Alzheimer's disease and Parkinson's disease.