Galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide/cyclic GMP pathway in vivo in the rat ventral hippocampus.

We investigated whether the neuropeptide galanin affects the nitric oxide synthase/cyclic GMP pathway in rat hippocampus by measuring in vivo the extracellular cyclic GMP levels during microdialysis. Galanin (2.5 and 3.5 nmol; i.c.v.) dose-dependently raised the extracellular levels of cyclic GMP in the ventral but not the dorsal hippocampus. The effect of 3.5 nmol galanin was blocked by local application of tetrodotoxin and inhibited by the high-affinity galanin antagonist M40 (galanin-[1-12]-Pro3-[Ala-Leu]2-Ala amide). The non-competitive N-methyl-D-aspartate receptor antagonist dizocilpine maleate (30 microM infused into the ventral hippocampus or 0.2 mg/kg, i.p.) and the competitive one, 3-([R]-carboxypiperazin-4-yl)-propyl-phosphonic acid (50 microM infused), but not local perfusion of the AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (15 microM) abolished the galanin-evoked cyclic GMP response in the hippocampus. Inhibitors of nitric oxide synthase, L-Arg(NO2)-OMe.HCl and 7-nitroindazole monosodium salt, applied locally, blocked the galanin-induced increase in hippocampal extracellular cyclic GMP. This increase was also prevented by local application of 1H-(1,2,4)oxadiazolo(4,3a) quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase. The galanin receptors mediating the rise in cyclic GMP reside outside the hippocampus, as galanin (0.35-3 nmol) locally applied had no effect. The results provide in vivo evidence that galanin stimulates the N-methyl-D-aspartate receptor/nitric oxide synthase/cyclic GMP pathway in the ventral hippocampus, which may be of importance in memory processes.

Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens.

We investigated whether D1 dopaminergic receptors modulate in vivo acetylcholine output in the shell and core areas of rat nucleus accumbens using the microdialysis technique. Subcutaneous injection (1, 2 and 3 mg/kg) of the D1 agonist SKF 82958 enhanced acetylcholine output in both areas of the nucleus accumbens while the selective D1 antagonist SCH 39166 (0.15 and 0.30 mg/kg, s.c.) lowered it. Both SKF 82958 and SCH 39166 were more effective in the shell than in the core region. The increase in acetylcholine release induced by SKF 82958 in the shell was tetrodotoxin-sensitive. The dopamine release inducer d-amphetamine (1 and 2mg/kg, s.c.) and the dopamine uptake inhibitor cocaine (10 and 20 mg/kg, i.p.) dose-dependently raised acetylcholine release in the shell and core areas. The dopaminergic stimulants, like the direct-acting D1 compounds, were more effective in the shell than in the core compartment of the nucleus accumbens. The acetylcholine increases in the shell induced by d-amphetamine (2 mg/kg), cocaine (20 mg/kg) and SKF 82958 (3 mg/kg) were antagonized by the D1 antagonists SCH 39166 (5 microM) and SCH 23390 (10 microM), applied locally by reverse dialysis. The results suggest that dopamine acting at the D1 receptors exerts a tonic stimulatory control over the cholinergic function of the shell and core compartments of the nucleus accumbens with the shell being more strongly influenced.

Effects of repeated oral doses of dexnorfenfluramine on 5-HT levels and 5-HT uptake sites in rat brain.

The effects of oral dexnorfenfluramine (DNF; 1-4 mg/kg, twice daily for 4 days), the active metabolite of dexfenfluramine, were examined on rat regional brain indole contents and [3H]citalopram binding. Two hours after the last dose, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were dose-dependently lowered at doses above 1.5 mg/kg, with slight regional differences. Cortical 5-HT uptake sites were reduced only at the highest dose. Above 2 mg/kg DNF also caused a more lasting reduction (4 weeks) of regional indoles and cortical 5-HT uptake sites. At this longer time while the decrease in hippocampal 5-HT levels and cortical 5-HT uptake sites remained essentially constant, cortical and striatal 5-HT levels were lowered less than at 2 h, suggesting a return toward control values.

Surgical anaesthesia with pentobarbital prevents the effect of local SCH 23390 on rat striatal acetylcholine release in a strain-dependent manner.

This study was performed in order to clarify existing discrepancies about the ability of the D1 antagonist SCH 23390 to reduce striatal acetyicholine (ACh) release after intrastriatal application by reverse dialysis. The possibility that negative findings were related to the use of pentobarbital rather than Equithesin as surgical anaesthesia for implanting microdialysis probes, and of Wistar rather than Sprague-Dawley rats, was tested. SCH 23390, applied by reverse dialysis at the concentration of 24µM, although able to reduce dialysate ACh in male Wistar rats implanted under Equithesin anaesthesia, failed to do so in rats of the same strain implanted 24h or 3 days earlier under pentobarbital anaesthesia. In male Sprague-Dawley rats, local SCH 23390 (24µM) reduced striatal dialysate ACh, both in rats implanted under Equithesin as well as in rats implanted under pentobarbital anaesthesia. Systemic SCH 23390 (0.3mg/kg s.c.) reduced dialysate A Ch both in Wistar and in Sprague-Dawley rats implanted under pentobarbital anaesthesia, but was more effective in the Sprague-Dawley strain. These observations, although consistent with a striatal localization of D1-receptors controlling ACh release, can be explained as being the result of a strain-dependent barbiturate-induced inactivation of D1-mediated control of ACh transmission, which is potentiated by the local changes induced by microdialysis probe implant.

MRI assessment of ventricular function.

Cine-MRI is a robust non invasive technique able to assess regional and global systolic function of both ventricles. Conventinal cine-MRI was used for LV global function parameters both on horizontal long axis and vertical long axis, applying area-length methods, as in echocardiography. Recent developments of segmented k-space techniques allowed breath-held cine-MRI, making possible a rapid acquisition of the entire ventricles, both left and right. Using the Simpson's rule volumes are estimated with high accuracy, without any geometrical assumption; this method is considered gold standard for global function assessment. Regional function is studied by cine-MRI both qualitatively and quantitatively, as it represents the best technique in defining endo- and epi-cardial borders. The ability of quantify wall thickness and wall thickening makes cine-MRI highly suitable for stress-imaging, both in ischemia detection and viability assessment. Tagging is a novel technique, able to assess the complex mechanism of myocardial contraction and to quantify myocardial strain. Finally MRI is also able to assess diastolic function with phase velocity mapping.