RESUMEN
RATIONALE: Repeated administration of psychostimulants such as amphetamine (AMPH) produces an enduring augmentation of their locomotor effects. Previous research suggests that this phenomenon, termed sensitization, is related to changes within the mesolimbic dopamine (DA) system. OBJECTIVES: The present experiments were designed to investigate the contribution of endogenous cholecystokinin (CCK), a neuropeptide co-localized with DA in the mesolimbic system, to the development (experiment 1) and the expression (experiment 2) of locomotor sensitization to AMPH. METHODS: In experiment 1, rats were injected (IP) with the CCK(A) antagonist devazepide (0, 0.001, 0.01, or 0.1 mg/kg) or the CCK(B) antagonist L-365,260 (0, 0.001, 0.01, 0.1, or 1.0 mg/kg) followed by AMPH (1.5 mg/kg) once daily for seven days. Following 10 days withdrawal, rats were administered AMPH (0.75 mg/kg) and their locomotor activity recorded. In experiment 2, rats were administered AMPH (1.5 mg/kg) once daily for 7 days. Following 10 days withdrawal, rats were injected with devazepide (0, 0.0001, 0.001, 0.01, 0.1, or 1.0 mg/kg) or L-365,260 (0, 0.001, 0.01, or 0.1 mg/kg) followed 30 min later by AMPH (0.75 mg/kg) and their locomotor activity recorded. RESULTS: When administered during the AMPH pretreatment phase of experiment 1, the two highest doses of L-365,260 attenuated, and the lowest dose of L-365,260 potentiated, the sensitized locomotor response to AMPH challenge. When administered prior to the AMPH challenge phase of experiment 2, devazepide attenuated the sensitized locomotor response to AMPH. CONCLUSIONS: These results suggest that CCK(B) and CCK(A) receptors modulate the development and the expression of behavioral sensitization to AMPH, respectively.
Asunto(s)
Anfetamina/farmacología , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Colecistoquinina/farmacología , Animales , Benzodiazepinonas/farmacología , Devazepida/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Compuestos de Fenilurea/farmacología , Ratas , Ratas Wistar , Receptor de Colecistoquinina A , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/antagonistas & inhibidoresRESUMEN
Serum thyroperoxidase (TPO) and serum human thyroglobulin (hTg) were studied in 80 patients with differentiated thyroid carcinoma after thyroidectomy before and after the first therapeutic radioiodine application ("radioiodine thyroid ablation") and, in some cases, after the second radioiodine application. Eighteen patients with an autonomous adenoma were studied in the same manner. The values of TPO and hTg in 25 persons without thyroid impairment were used as controls. In 34 of 50 evaluable cases, TPO levels behaved as hTg during follow-up studies: The majority (n= 30) of these patients showed an increase in TPO and hTg serum levels immediately after radioiodine therapy, followed by a decrease approximately 3 days later. However, in 16 of 50 patients, the TPO and hTg serum levels showed different patterns of change both before and after radioiodine therapy. In six of seven patients with extensive postoperative residues and high anti-hTg levels, distinctly elevated TPO values were associated only by slightly elevated thyroglobulin values. There was no rise of TPO in autonomous adenoma except in patients treated with thyroid depressants. We assumed that TPO levels could serve as an "indicator" for destruction of thyroid cells or thyroid carcinoma cells and an aid in screening cases of false-negative hTg values.
Asunto(s)
Adenocarcinoma Folicular/diagnóstico , Adenoma/diagnóstico , Biomarcadores de Tumor/sangre , Carcinoma Papilar/diagnóstico , Pruebas Enzimáticas Clínicas , Yoduro Peroxidasa/sangre , Radioisótopos de Yodo/uso terapéutico , Metástasis de la Neoplasia/diagnóstico , Proteínas de Neoplasias/sangre , Recurrencia Local de Neoplasia/diagnóstico , Tiroglobulina/sangre , Neoplasias de la Tiroides/diagnóstico , Adenocarcinoma Folicular/patología , Adenocarcinoma Folicular/radioterapia , Adenocarcinoma Folicular/cirugía , Adenoma/patología , Adenoma/cirugía , Anciano , Antitiroideos/uso terapéutico , Carcinoma Papilar/patología , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirugía , Diferenciación Celular , Terapia Combinada , Reacciones Falso Negativas , Femenino , Estudios de Seguimiento , Humanos , Radioisótopos de Yodo/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/enzimología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Periodo Posoperatorio , Radioterapia Adyuvante , Sensibilidad y Especificidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment.
Asunto(s)
Anfetamina/farmacología , Dopaminérgicos/farmacología , Actividad Motora/efectos de los fármacos , Receptores de Colecistoquinina/fisiología , Análisis de Varianza , Animales , Masculino , Ratas , Ratas Wistar , Receptor de Colecistoquinina ARESUMEN
We have previously shown that individual differences in oral sucrose consumption are predictive of behavioral reactivity of rats in the elevated plus-maze (EPM). The present experiments were designed to replicate the EPM results and to extend them to another animal model of anxiety, the acoustic startle reflex (ASR) paradigm. In two experiments, sucrose consumption was assessed in separate groups of rats across eight daily 1-h feeding sessions. Animals were designated as either low (LSF) or high sucrose feeders (HSF) based on a median split of their sucrose intake on the final test day. Following this assay, animals were tested in the EPM in Experiment 1, and in the ASR paradigm in Experiment 2. Results from Experiment 1 replicated our previous findings and showed that the percentage of time spent on, and entries into, open arms was significantly lower in LSF than HSF. Further, results from Experiment 2 revealed a significantly augmented startle response to acoustic stimuli (94-108 dB SPL) in LSF compared to HSF. These data provide converging evidence to support the notion that individual differences in baseline levels of oral sucrose consumption are predictive of anxious behaviors in rats.
Asunto(s)
Ansiedad/psicología , Conducta Animal/fisiología , Sacarosa en la Dieta , Ingestión de Alimentos/psicología , Estimulación Acústica , Alimentación Animal , Animales , Individualidad , Masculino , Ratas , Ratas Wistar , Reflejo de Sobresalto/fisiologíaRESUMEN
Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes.