| Objective: Schedule-induced polydipsia (SIP) is a phenomenon whereby excessive drinking is produced when food-deprived rats are given small food rewards intermittently with water freely available. When the body weights of rats are reduced to 80% of their normal levels, the rats are allowed to obtain a small pellet of food on an interval of 1-min schedule for 3 h each day. After the treatment, rats will consume excessive amounts of water. Normally, a rat drinks only about 20 ml of water within 24 h, but the rat with SIP drinks up to 90 ml within 3 h. The mechanisms of SIP are complicated, which may widely involve neural activity, stress, anxiety, emotion and so on. SIP is only one of the observed excessive behaviors, and may share the common underlying mechanisms of the other excessive behaviors such as drug addiction. The neurotransmitters dopamine (DA), serotonin (5-HT) and norepinephrine (NE) are known to be related to the manifestation of this behavior. To our knowledge, the effect of the glutamatic system on SIP has not been reported so far. In this study, we investigated the potential role of glutamatic system by administering MK-801, a NMDA receptor antagonist, centrally and peripherally in SIP rats. In addition, the neuronal nitric oxide synthase (nNOS) expression was detected by the immunostaining (labeled avidin-biotin method) to reveal the influence of MK-801 to nNOS activity. The results showed that MK-801 impairs theSIP behavior in rats, providing new evidence for the role of the glutamic system on SIP. Our study is valuable for the further researches on SIP and the understanding of the biological mechanism(s) of excessive behaviors.Methods and Results:1. The control of the rat body weightsThe body weights of all rats used in the experiments were reduced to 80% of their normal weights by the restricted food supply. The reduced body weights were kept as stable as possible during the experiments. For the rats whose body weights were less than 80% of their original values, they were adjusted by an increased food supply, and for those with larger weights by a decreased food supply.2. The establishment of SIP behaviorThe scheduled training process was done once at each session for 3 h daily. The rats were put into a special cage 15 min before the process began. The food supply during the training process was controlled by a computer, and the food supplier provided a small pellet of food on an interval of 1-min. The volume of supplied water was recorded at the beginning and the ending point of the training process. The consumed volume of water during the training process was calculated from the difference of two recordings. More than 95% of the rats had established their stable SIP behavior after a 4-day training program. They consumed significantly an increased volume of water (P < 0.01).3. The effect of MK-801 on SIP by systematic injectionStable SIP rats were systematically injected with MK-801 (0.125 mg kg-1, ip) 15 min before the experiment, while control rats were injected with a same volume of saline. The volume of the consumed water during the 3-h experiment was recorded. The results showed that MK-801 (0.125 mg kg-1, ip) significantly inhibited the SIP behavior in rats (P < 0.05).4. The effect of MK-801 on SIP by intracerebral injectionStable SIP rats were given an intracerebral injection of MK-801 (3.5, 7.0, 14.0 g) into prefrontal cortex (AP = 3.2 mm, ML = 0.6 mm, DV = -3.2mm), nucleus accumbens (AP = 1.6 mm, ML = 1.5 mm, DV = -7.5 mm) and amygdala (AP = -1.8 mm, ML = 3.5 mm, DV = -8.3 mm) respectively. The volume of the consumed water during the 3-h experiment was recorded. The results showed that MK-801 (3.5, 7.0, 14.0 g) dose-dependently inhibited the SIP behavior (P < 0.05 - 0.01).5. The effect of MK-801 on nNOS expression in the brain regions of the ratsIn frozen sections from the rats, nNOS immunopositive neurons were detected by a labeled avidin-biotin method. We found that the number of nNOS positive neurons increased in the prefrontal cortex,...
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