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Anxiety but not arousal increases 5-HT release in rat hippocampus
Objectives: The central serotonergic system is involved in the aetiology of numerous disease states, including depression and anxiety disorders. Drugs that alter serotonin (5-HT) function are the frontline treatment of anxiety disorders. Several studies have shown that exposure of rats to animal tests for anxiety increases extracellular 5-HT in the cortex or the hippocampus.
Aim of the study is to discriminate whether the increase in extracellular 5-HT is caused by aversive conditions of an animal test for anxiety or by an unconditioned stressor evoking arousal.
Methods: The present study investi¬gates the effects of exposure to an acoustic stimulus (95 dB) or to the ele¬vated plus maze (X-maze, illumination: 210 lux open arms, 160 lux closed arms) or to a X-maze with closed arms only (C-maze), for 20 minutes respectively, on 5-HT relea¬se in the ventral hippocampus of rats, determined by in vivo microdialysis followed by HPLC and electrochemical detection.
Results: Exposure of male Fischer 344 rats (Charles River, Germany, 220±30 g) to the X-maze induced an ‘anxious’ behaviour and increased extracellular 5 HT to 165% of basal release. However, exposure to white noise in the familiar surroundings of the home cage did not change extracellular 5-HT in the hippocampus, even though locomotor activity and the percentage of animals digging in the bedding were increased.
Conclusions: The increased 5-HT release concurred with exposure to the X maze but not to the less aversive but new surroundings of the C-maze with or exposure to white noise. This indicates a strong relationship between 5-HT release and behaviour indicative of "anxiety". Our results are backed up by recent studies showing ‘anxiolytic’ effects of Neuropeptide S accompanied by increased motor activity. It is suggested that the relationship between arousal/non-specific behavioural activation and 5-HT in general is not necessarily linked in the rat hippocampus.