Poster Session - Neurophysiology: neurotransmitters P741 The influence of sodium oxybate and sleep on reward processing: an fMRI study J. HOFMEISTER, V. STERPENICH, K. IGLOI, M. DESSEILLES, M. GSCHWIND and S. SCHWARTZ University of Geneva, Geneva, CH Objective: Sodium oxybate (SO; Xyrem Ò ) has been approved in most countries for treatment of narcolepsy with cataplexy. It acts as a GABA(B) receptor agonist, improving disrupted sleep, decreasing sleep onset latency, and increasing slow waves activity (SWA) in narcoleptic patients as well as in healthy subjects. Here, we tested (1) whether SO influences brain network related to reward processing and (2) whether changes in sleep induced by SO affect reward processing in healthy subjects on the next day. Method: Nineteen subjects were given SO or placebo (PL) over two distinct fMRI sessions. Each subject performed a game-like task after SO/PL administration in an evening session (1). PSG was recorded in the following night. On the next day, a second session of game-like task was performed during the afternoon (2). During the game-like task, subject could win or lose points by rapidly detecting a target. We compared brain activity during winning or losing points after SO or PL, during the evening session and after the sleep. Results: At behavioural level, subjects detected the target more rapidly after negative cues (potential losses) immediately after SO, suggesting increased risk aversiveness in these subjects. Subjects also often pressed too early under SO for positive cues (potential gains), suggesting an increased impulsivity for obtaining rewards. After one night of sleep under SO (versus PL), we observed no other modification in reaction times. At the fMRI level, during the evening session, subjects under direct influence of SO (as compared to PL) showed significant activation in an error monitoring network (including the anterior cingulate) when they are losing for cues signaling large potential gains, and activated significantly more a network related to reward processing (including the ventral putamen) when they are actually winning for these same cues, suggesting that SO enhances reward sensivity. After a night of sleep modified by SO (versus PL), we found a significant activation of the bilateral amygdala and right insula when subjects lost large amounts of points, suggesting that changes in sleep after SO administration may have an effect on error processing and emotional reactivity on the next day. The analysis of sleep data will be also presented. Conclusion: SO (as compared to PL) influences reward functions at both the behavioral and brain level. This work is supported by UCB P742 Sleep and motor function after GHB and baclofen administration in healthy rats and rats with focal cerebral ischaemia A. HODOR, S. PALCHYKOVA, B. GAO and C. BASSETTI University Hospital of Berne, Berne, CH Objectives: There is still no effective treatment available for stroke patients. Promotion of neuroplasticity during recovery may represent an alternative therapeutic strategy. Sleep has been implicated in facilitation of neuroplasticity. Sleep promoting drugs, gamma-hydrox- ybutyrate (GHB) and baclofen (Bac), administered during the acute phase after ischemia showed neuroprotection. We investigated (1) changes in sleep induced by GHB and Bac in healthy rats, (2) stroke outcome following Bac administration beyond the acute phase in a rat model of focal cerebral ischemia. Methods: (1) Adult male rats (n = 26) were implanted with EEG/ EMG electrodes. GHB (150 or 300 mg/kg), Bac (10 or 20 mg/kg) or saline were administered 1 h after light onset and offset. (2) Rats subjected to middle cerebral artery occlusion (MCAo) were treated with Bac (10 mg/kg) or saline. First injection, done 24 h after MCAo, was followed by two daily injections during 10 consecutive days. Animals were assigned to the ischemia/Bac, sham/Bac or ischemia/ saline group (n = 8 per group). Functional recovery was evaluated by single pellet reaching test (SPR). Results: (1) GHB and Bac caused abnormal behavior (immobile flat body posture, limbs stretched sideways, eyes opened) and physiol- ogy (hypersynchronous slow waves in EEG) lasting up to 413 min. Amount of vigilance states was evaluated after the end of the abnormal state. Bac increased NREM sleep in the light and dark phase (16 and 91 min, respectively; P < 0.05, paired t-test). REM sleep was enhanced by 12 min in the dark (P < 0.05). Time of Bac administration affected NREM sleep episode duration and frequency. Thus, during the light phase Bac increased the duration of NREM sleep episodes (P < 0.01), but reduced their frequency (P < 0.05), while during the dark phase only episode frequency was increased (P < 0.0001). GHB had no effect on vigilance states. EEG spectral analysis is in progress. (2) SPR performance dropped to 0 imme- diately after MCAo in both ischemic groups and recovered slowly in the course of 1.5 month. Bac-treated ischemic rats showed slightly better performance than saline-treated rats, but the group difference did not reach statistical significance. The data collection is ongoing. Conclusion: Our results indicate that GHB and Bac induced sub- anesthetic state distinct from physiological sleep, confirming previ- ously published mouse data. Bac treatment increased the amount of sleep after the end of drug-induced state. This study was supported by UCB Pharma S.A. Belgium, Alle ´ e de la Recherche, 60, B - 1070 Brussels P743 Metabolic effects of sodium oxybate G. LUCA and M. TAFTI University of Lausanne, Lausanne, CH Gammahydroxybutyrate (GHB) (sodium oxybate, Xyrem Ò ), is used in sleep medicine for the treatment of narcolepsy with cataplexy. One of the side effects observed in treated patients is weight loss. Aim: To investigate metabolic changes after acute, short-term and chronic administration of GHB in different mouse strains. Methods: In four different experiments we have evaluated both the acute and chronic metabolic changes induced by the drug. For acute metabolic changes blood was assessed at 1h after the drug administration. In a second step, mice were studied in the calori- metric chambers for 8 days: 4 baseline days and 4 days under drug administration, in randomized order. Food and water intake, respi- ratory ratio (RER), oxygen consumption and CO2 production, locomotor activity and weight were measured. For chronic metabolic changes mice were studied 4 weeks under placebo or 300 mg GHB/ kg/day. Lean mass, fat mass, and water content were assessed by ª 2012 The Authors Journal of Sleep Research ª 2012 European Sleep Research Society, JSR 21 (Suppl. 1), 1–371 Poster Session - Neurophysiology: neurotransmitters 259 View publication stats View publication stats