Resumo

Introduction: Among the stress effects on normal physiology, significant sleep pattern changes are a common finding, including insomnia and alterations in the specific sleep phases. The increase in REM sleep that follows exposure to stress has been considered as recovery factor, and some authors hypothesize that this phenomenon may prevent the development of post-traumatic stress disorder. In addition to the classical stress hormones, prolactin (PRL), which is released after stressful events and acts on the regulatory sleep-wake mechanisms, may be a candidate mediator of these effects of stress on sleep. Objective: To evaluate the effects of prolactin infusion in the dorsal raphe nucleus (a major structure for sleep regulation and hypothalamic function) in the Wistar rats sleep-wake cycle. Methodology: Adult male rats (400 ± 50 g) were surgically implanted with electroencephalographic (EEG) and electromyographic (EMG) electrodes and a cannula was inserted into the dorsal raphe nucleus region. Animals were submitted to recording of their sleep-wake cycle, before and after the infusion of PRL into the dorsal raphe. All animal procedures were approved by our local Research Ethics Committee in accordance with international guidelines for care in animal research (Universidade Federal de São Paulo - CEP 1848/09). After two days (2 x 24h) of recordings to determine and the baseline sleep pattern, half of the animals (n=4) were infused with 0.3 μL of artificial cerebral spinal fluid (aCSF), whereas the other half (n=4), received 1 ng of PRL (Sigma, USA), at the same volume and region (dorsal raphe nucleus). Infusions were performed at 07:00 AM. Henceforth, animals had their sleep-wake cycle recorded for 48 h, and then, were sacrificed and submitted to histological confirmation of the infusion site. All electrophysiological recordings were scored manually in 10 s epochs. Results were analyzed by Student’s t-test and two-way ANOVA for repeated measures (treatment and period) followed by Newman-Keuls post-hoc test, when necessary. The level of significance was set at p < 0.05. Results: During the first 12 h after infusion (light period), rats which received PRL exhibited an expressive increase in the total time of REM sleep (144.8%; p≤0.01). Duration of REM sleep episodes was also increased in these animals (PRL: 2.372 ± 0.09min., aCSF: 1.822 ± 0.03min., p≤0.001). Interesting to notice is the fact that the increase in the amount of REM sleep began after the third hour after infusion (10:00-13:00h: 138.94%; p≤0.03), lasting for the entire light period (13:00-16:00h: 112.75%; p≤0.05 e 16:00-19:00h: 112.27%; p≤0.05). A similar pattern occurred with the duration of REM sleep episodes (10:00-13:0h: 54.95%; p≤0.04; 13:00-16:00h: 64.45%; p≤0.02). Conclusions: The infusion of PRL in the dorsal raphe nucleus produced an increase in REM sleep. Given that PRL causes an immediate release of serotonin from the dorsal raphe, and that the increase in REM sleep took place only 3 hours after infusion it is possible that genomic transcription mechanisms, involving other mediators (possibly through serotonergic pathways to hypothalamus), may be implicated in this phenomenon. Finnancial Support: Associação Fundo de Incentivo à Psicofarmacologia - AFIP; FAPESP-CEPID (#1998/14303-3); CNPq.