Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was potently antagonized by the administration of the D1 selective antagonist SCH 23390 and by the opioid antagonist naloxone. In this paper we show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain area. These data suggest an active role of limbic dopamine and opioid systems in the generation of arousal and insomnia related to sleep deprivation-induced stress.