Nociceptin/orphanin-FQ (NOCI) together with its receptor NOP are widely expressed in cortical and subcortical motor areas and it is known that NOCI acts as an anxiolytic attenuating the behavioral inhibition of animals acutely exposed to stressful/anxiogenic conditions. Influence of NOCI upon the dopaminergic system has been observed in the ventral tegmental area and in the nucleus accumbens as well as an inhibitory action of NOCI is described upon serotoninergic mechanisms at cells and terminal levels. In particular, it is known that serotoninergic fibers from the raphe system project to the substancia nigra (SN) and that this modulation is behaviourally relevant. In the present work, the effect of exogenous NOCI injected into the SN upon DA and 5-HT levels have been analyzed by means of differential pulse voltammetry and nafion-carbon fiber microelectrodes. Electrophysiological monitoring of multicell activity was concomitantly performed with the same microsensor. It appeared that both levels of these biogenic amines were specularly altered, with possibly a driving influence of the DA activity upon the serotoninergic function(s). Show less

Aims Cardiac autonomic neuropathy is currently an untreatable progressive complication of type 1 diabetes (T1D). Impaired microcirculation is a suspected cause of nerve degeneration in TID. We investigated whether cardiovascular autonomic reflexes often used as indices of nerve functions, are associated with indices of microcirculatory function in young adults with T1D compared with non-diabetic controls. Methods In a cross-sectional study, 15 adults with T1D and 15 age-matched controls (20-40 years) underwent standardized cardiovascular autonomic reflex tests. Continuous recordings of electrocardiogram, cardiac vagal tone, beat-to-beat blood pressure and transcutaneous tissue oxygen (tcpO₂) and carbon dioxide partial pressures (tcpCO2) were done. Results Despite preserved baroreflex, parasympathetic, and sympathetic functions assessed using cardiovascular reflex tests, the individuals with T1D exhibited reduced baseline tcpO2 compared to the controls (37.5±3.75 vs. 49.6 mmHg). During the Valsalva manoeuvre, individuals with T1D exhibited a reduced systolic blood pressure response in phase I (31±10 vs. 43±18 mmHg) and early phase II (-1±15 vs. -18±17 mmHg), and an increased systolic (31±15 vs. 18±14 mmHg) and diastolic (45±11 vs. 33±16 mmHg) response in late phase II compared to controls. The early phase II diastolic response was inversely associated with baseline tcpO2. Conclusion The altered hemodynamic response to the Valsalva manoeuvre is suggestive of possible reduced arterial elasticity, higher vascular resistance, and splanchnic sympatho-vagal imbalance in T1D despite normal autonomic reflex ratios. The concomitant evidence of reduced tissue oxygenation and altered hemodynamics may represent early signs of dysautonomia but require longitudinal validation.   Show less