Serotonin 5-HT 1A receptors constitute an attractive therapeutic target for various psychiatric or neurodegenerative disorders. These receptors are expressed in multiple brain regions on different neuronal populations and can be coupled with distinct G-protein subtypes; such functional diversity complicates the use of 5-HT 1A ligands in several pathologies where it would be desirable to stimulate the receptors in a precise region. Therefore, using "biased agonists" able to target specifically certain subpopulations of 5-HT 1A receptors would enable achievement of better therapeutic benefit. Several 5-HT 1A receptor biased agonists are currently in development, including NLX-101 (aka F15599) and NLX-112 (aka F13640, befiradol), with preclinical data suggesting that they preferentially target different populations of 5-HT 1A receptors. However, most previous studies used invasive and regionally limited approaches. In this context, [ 18 F]-fluorodesoxyglucose (FDG)-positron emission tomography (PET) imaging constitutes an interesting technique as it enables noninvasive mapping of the regional brain activity changes following a pharmacological challenge in conscious animals. We report here the evaluation of cerebral glucose metabolism following intraperitoneal injection of different doses of NLX-112 or NLX-101 in conscious or isofluraneanesthetized rats. The biased agonists produced different metabolic "fingerprints" with distinct regional preferences, consistent with previous studies. At equal doses, the effect of NLX-101 was less marked than NLX-112 in the piriform cortex, in the striatum (in terms of inhibition), and in the pontine nuclei and the cerebellum (in terms of activation); furthermore, only NLX-112 increased the glucose metabolism in the parietal cortex, whereas only NLX-101 induced a clear activation in the colliculi and the frontal cortex, which may be related to its distinctive procognitive profile. Both agonist effects were almost completely unapparent in anesthetized animals, underlining the importance of studying serotonergic neurotransmission in the conscious state. In this regard, [ 18 F]FDG-PET imaging seems very complementary with other functional imaging techniques such as pharmacological MRI.

Centers failing to meet the minimum standards for workload should consider their position in relation to standards and NICE guidance (UKCS, NICE). In particular, departments should give attention to standards described in "Good Urodynamic Practice," establish multi-disciplinary teams for continence management and consider greater centralization of investigations for patients with neuropathies and for ambulatory studies. Most staff attended a course, yet few can describe how to zero transducers. This raises questions about the quality of reporting of some urodynamic studies. Those that are involved in urodynamics should take part in regular CME, relevant audit and consider certification and revalidation. This audit has highlighted significant variations in practice and lends support to the application of nationally agreed standards.

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