RESUMEN
Alcohol has a wide variety of effects on physiology and behavior. One of the most well-recognized behavioral effects is disinhibition, where behaviors that are normally suppressed are displayed following intoxication. A large body of evidence has shown that alcohol-induced disinhibition in humans affects attention, verbal, sexual, and locomotor behaviors. Similar behavioral disinhibition is also seen in many animal models of ethanol response, from invertebrates to mammals and primates. Here we describe several examples of disinhibition in the nematode C. elegans. The nematode displays distinct behavioral states associated with locomotion (crawling on land and swimming in water) that are mediated by dopamine. On land, animals crawl and feed freely, but these behaviors are inhibited in water. We found that additional behaviors, including a variety of escape responses are also inhibited in water. Whereas alcohol non-specifically impaired locomotion, feeding, and escape responses in worms on land, alcohol specifically disinhibited these behaviors in worms immersed in water. Loss of dopamine signaling relieved disinhibition of feeding behavior, while loss of the D1-like dopamine receptor DOP-4 impaired the ethanol-induced disinhibition of crawling. The powerful genetics and simple nervous system of C. elegans may help uncover conserved molecular mechanisms that underlie alcohol-induced disinhibition of behaviors in higher animals.
Asunto(s)
Conducta Animal/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Etanol/farmacología , Animales , Dopamina/farmacología , Locomoción/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Fenómenos Fisiológicos del Sistema Nervioso/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Natación/fisiologíaRESUMEN
A magnetic resonance (MR) technique is developed to produce controlled radio-frequency (RF) hyperthermia (HT) in subcutaneously-implanted 9L-gliosarcoma in Fisher rats using an MR scanner and its components; the scanner is also simultaneously used to monitor the tumour temperature and the metabolic response of the tumour to the therapy. The method uses the (1)H chemical shift of thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (TmDOTA(-)) to monitor temperature. The desired HT temperature is achieved and maintained using a feedback loop mechanism that uses a proportional-integral-derivative controller. The RF HT technique was able to heat the tumour from 33 degrees to 45 degrees C in approximately 10 min and was able to maintain the tumour temperature within +/-0.2 degrees C of the target temperature (45 degrees C). Simultaneous monitoring of the metabolic changes with RF HT showed increases in total tissue and intracellular Na(+) as measured by single-quantum and triple-quantum filtered (23)Na MR spectroscopy (MRS), respectively, and decreases in intra- and extracellular pH and cellular bioenergetics as measured by (31)P MRS. Monitoring of metabolic response in addition to the tumour temperature measurements may serve as a more reliable and early indicator of therapy response. In addition, such measurements during HT treatment will enhance our understanding of the tumour response mechanisms during HT, which may prove valuable in designing methods to improve therapeutic efficiency.