P. de Boer

The effect of surface roughening of polymers on measured contact angles of liquids

Equilibrium, advancing and receding contact angles for five different liquids have been determined on twelve commercial polymers after various surface roughening procedures. It was found that influences of surface roughening on contact angles disappear if the stylus surface roughness RA is < 0.1 μm. Surface roughening tends to increase observed contact angles, if the contact angle on the smooth surface is above 86°, whereas contact angles decrease if the contact angle on the smooth surface is below 60°. For contact angles on the smooth surface between 60° and 86°, surface roughening was found not to influence measured contact angles. These results show a broad similarity in the trend, predicted by the early Wenzel equation, describing the influence of surface roughness on contact angles, although of course the stylus surface roughness RA is not identical to the theoretical r-parameter in the Wenzel equation.

Ascending projections from the solitary tract nucleus to the hypothalamus. A Phaseolus vulgaris lectin tracing study in the rat

The course of the ascending pathways originating from the anterior gustatory and posterior visceral sensory part of the solitary tract nucleus and the topographic organization of the projections to the hypothalamus in the rat were studied with anterogradely transported Phaseolus vulgaris lectin. In general, the posterior visceral sensory part of the solitary tract nucleus has ascending projections as far as the septum-diagonal band complex and gives rise to heavy input to the bed nucleus of the stria terminals, and to the dorsomedial and paraventricular hypothalamic nuclei. A more moderate projection is aimed at a variety of other hypothalamic nuclei, to the medial and central amygdaloid nuclei and to the paraventricular nucleus of the thalamus. The ventromedial hypothalamic nucleus is strikingly missing an afferent input from the nucleus of the solitary tract. Furthermore, it was shown that whereas the caudal solitary tract nucleus has predominant long ascending connections, the projections from the anterior taste related region of the nucleus of the solitary tract have only limited forebrain projections which do not reach beyond the level of the anterior dorsal hypothalamic nucleus.

Basal acetylcholine release in freely moving rats detected by on-line trans-striatal dialysis: Pharmacological aspects

The basal release of acetylcholine (without the use of an esterase inhibitor) from brain tissue was quantified by means of transversal striatal dialysis in freely moving rats, coupled on-line to an HPLC analysis system. Basal release of acetylcholine was shown to be fully calcium dependent and tetrodotoxin sensitive. A comparison between a U-shaped and a transversally localized dialysis probe was made and some important differences were noticed. The use of a transversal probe resulted in a 20 times higher recovery when compared with the U-shaped cannula. The effect of the cholinomimetic oxotremorine and the anticholinergic atropine on the basal acetylcholine output was determined. Atropine increased the output of acetylcholine, whereas oxotremorine induced a decrease in the output of the transmitter. Application of various degrees of esterase inhibition (by addition of neostigmine to the perfusion fluid) did not qualitatively interfere with the effects of oxotremorine or atropine on the release of acetylcholine.

Antipsychotic drugs induce similar effects on the release of dopamine and noradrenaline in the medial prefrontal cortex of the rat brain.

In the present study we have compared the effects of the classical antipsychotic drug haloperidol and four different atypical antipsychotics (clozapine, risperidone, olanzapine, ziprasidone) on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex (MPFC) of conscious rats. Haloperidol (10, 100 and 800 nmol/kg), clozapine (0.3, 1, 10 and 30 micromol/kg), risperidone (100, 500 and 5000 nmol/kg), olanzapine (10, 100 and 500 nmol/kg) and ziprasidone (10, 100 and 1000 nmol/kg) were administered subcutaneously to rats. All compounds induced increases in dialysate levels of dopamine and noradrenaline in the medial prefrontal cortex. The increases induced by the four antipsychotic agents in extracellular levels of dopamine and noradrenaline displayed a striking co-variation both in dose and time. A similar co-variation was seen in the decrease of dopamine and noradrenaline, after administration of a low dose (30 nmol/kg, s.c.) of the dopamine D2/3 receptor agonist (+)-7-hydroxy-2-(N,N-di-n-propylamino) tetralin ((+)-7-OH-DPAT). It is concluded that there is a close coupling between the release of dopamine and noradrenaline in the medial prefrontal cortex. The mechanism of action of this interaction, that might be of importance for a better understanding of the mechanism of action of antipsychotic drugs, is discussed.

Dopaminergic-cholinergic interactions in the striatum : the critical significance of calcium concentrations in brain microdialysis

SummaryBrain microdialysis experiments were performed to assess the effects of calcium (1.2 mmol/l and 3.4 mmol/l) in the perfusio solution on a variety of pharmacological treatments known to affect the release of dopamine (DA) and/or acetylcholine (ACh). Intrastriatal infusion of the muscarinic receptor agonist oxotremorine (100 μM), the selective dopamine D-2 receptor agonist (−)-N-0437 (1 μM), and the indirect DA agonists (+)amphetamine (10 μM) and nomifensine (1 μM) via the dialysis probe did not affect the overflow of ACh when the perfusion fluid contained 3.4 mmol/l calcium. In contrast, these compounds produced pronounced decreases in the overflow of ACh at 1.2 mmol/l calcium. Intrastriatal infusion of the muscarinic receptor antagonist atropine (1 μM) increased the output of ACh both at 1.2 mmol/l and 3.4 mmol/1 calcium. The selective DA D-2 receptor antagonist (−)-sulpiride (1 μM) did not affect the overflow of ACh at either calcium concentration. Infusion of oxotremorine and atropine had no effect on the overflow of DA at either 1.2 mmol/l or 3.4 mmol/l calcium. (−)-N-0437 decreased and (−)-sulpirde increased DA overflow, both effects being independent of the calcium concentration in the perfusion fluid. Nomifensine and (−)amphetamine caused relatively (but not absolutely) larger increases in the overflow of DA at 1.2 mmol/1 calcium. These findings emphasize the critical importance of the calcium concentration of the perfusion fluid in determining the nature of pharmacological responses in microdialysis experiments, and demonstrate that locally applied dopaminergic drugs can modulate striatal cholinergic function.

The effect of intrastriatal application of directly and indirectly acting dopamine agonists and antagonists on the in vivo release of acetylcholine measured by brain microdialysis

SummaryThe effect of intrastriatal application of D-1, D-2 and indirect dopaminergic drugs on the release of striatal acetylcholine as a function of the post-implantation intervals was studied using in vivo microdialysis. The dopamine, D-2 agonists LY 171555 and (−)N0437 inhibited the release of striatal acetylcholine to 40% of control values 16–24 h after implantation of the dialysis cannula. When LY 171555 was infused 40–48 h after implantation of the dialysis cannula, the response was attenuated to 20% of control values. Meanwhile, the effectiveness of infusions of the antagonists (−)sulpiride and haloperidol was augmented from a non significant effect at 16–24 h to a 150% increase 40–48 h after implantation of the cannula.Infusions of the dopamine releasing agent amphetamine or the dopamine uptake inhibitor nomifensine resulted in a dose-dependent increase in the overflow of dopamine. Not until a sevenfold increase in the level of dopamine was seen, the release of acetylcholine was significantly affected. This hyporesponsiveness of the striatal cholinergic interneurons to endogenous dopamine could not be attributed to dopamine D-1 receptor activation, since no effects on striatal acetylcholine release were found by intrastriatal infusions of the selective D-1 agonist CY 208-243 or the selective D-1 antagonist SCH 23390.The results indicate that dopamine D-2 receptors are involved in the regulation of striatal acetylcholine release and that these receptors are tonically occupied by endogenous dopamine under the present experimental conditions 40–48 h after probe implantation. The fact that cholinergic responses to intrastriatally applied dopaminergic agents are dynamic with respect to the time between implantation surgery of the dialysis tube and the experimental measurements suggests that the striatal neuronal system is perturbated by the implantation of a dialysis probe for a considerable length of time.

DOPAMINE-ACETYLCHOLINE INTERACTION IN THE STRIATUM STUDIED BY MICRODIALYSIS IN THE AWAKE RAT - SOME METHODOLOGICAL ASPECTS

In order to evaluate the dopamine/acetylcholine balance hypothesis, sulpiride, (-)-N-0437, oxotremorine or physostigmine were administered intraperitoneally to rats, whereas the extracellular levels of acetylcholine and dopamine in the striatum were recorded by microdialysis. The changes in dialysate concentration of the transmitters did not support the supposed interaction between dopaminergic and cholinergic neurons. Next, we infused direct and indirect dopamine agonists such as (-)-N-0437, amphetamine and nomifensine via the dialysis membrane. The dopamine agonists had no effect on the release of acetylcholine when the calcium concentration of the perfusion fluid was 3.4 mmol/l, but the agonists effectively inhibited the release of the transmitter when the calcium concentration was 1.2 mmol/l. The cholinergic drugs physostigmine, oxotremorine, atropine did not affect the release of dopamine.

A laboratory evaluation of three etching solutions

Abstract Solutions containing 50 m/m % phosphoric acid (A), 25 m/m % pyruvic acid (B), and 50 m/m % citric acid (C) were prepared. The tensile bond strenghs of a conventional chemically activated composite resin (Concise) and a sealant (Delton) to enamel surfaces etched with the respective etching agents were determined. The surface roughness (RA) of polished enamel surfaces etched with the respective acids was measured and the effects on the morphology of polished etched enamel surfaces evaluated by SEM. The tensile bond strengths expressed in MN.m−2 were: Concise: Etched with A=15.2± 3.5; B=19.1±3.1;C=10.7±1.8. Delton: Etched with A=13.5±2.9; B =18.6±4.7; C=8.4±1.4. Pyruvic acid etching produced significantly greater bond strengths than phosphoric acid etching which in turn produced significantly greater bond strengths than citric acid. RA values in μm were: A= 0.31±0.07; B=0.33±0.05; C=0.17±0.03. Phosphoric acid and pyruvic acid etching of polished enamel surfaces produced well-defined etching patterns.

Characterization of the effect of dopamine D3 receptor stimulation on locomotion and striatal dopamine levels

By examining the effect of dopamine (DA) D3 receptor stimulation on locomotor activity and extracellular levels of DA in striatum we show that inhibition of locomotor activity induced by DA D3 receptor-selective agonists is mediated by two interacting mechanisms: (1) directly via the stimulation of DA D3 receptors that inhibit locomotor activity, and (2) indirectly via a decrease in extracellular levels of DA. Thus, the moderately DA D3 receptor-selective agonist R-(+)-7-OH- DPAT (R-(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin) decreased locomotor activity after administration of 10 nmol/kg and extracellular DA levels in accumbens and striatum after administration of 30 nmol/kg. A decrease in locomotor activity that coincided with a decrease in extracellular DA levels in striatum was observed after administration of 100 nmol/kg of the DA D3 receptor-selective agonist PD128907 ((+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3 b]-1,4-oxasin-9-ol. In combination with the partial, DA D3 receptor-selective agonist PD151328 (2-[4[3-(4-phenyl)-1- piperazinyl)propoxy]phenyl]-benzamidazole), a reversal of the attenuating effect of PD128907 on locomotor activity was observed, without an effect on extracellular levels of DA. In combination with a low--10 nmol/kg--dose of haloperidol, a reversal of the inhibitory effect of PD128907 on locomotor activity was observed that coincided with an increase in extracellular levels of DA. In the presence of 0.5 mg/kg amphetamine, PD128907 decreased amphetamine-induced locomotor activity. This effect could be reversed by PD151328.

Dopamine D-2 activity of R-(-)-apomorphine and selected analogs: a microdialysis study

In the present study, R-(-)-apomorphine and three of its analogs were studied for their potency in decreasing the release of dopamine in the striatum after subcutaneous administration and for their oral bioavailability using the microdialysis technique in freely moving rats. The analogs R-(-)-N-n-propylnorapomorphine and R-(-)-11-hydroxy-N-n-propylnoraporphine displayed a higher potency than R-(-)-apomorphine in decreasing the release of dopamine in the striatum. A high dose of R-(-)-11-hydroxyaporphine, a dopamine D(2) receptor partial agonist, had a small effect on the release of dopamine in the striatum. The catechols R-(-)-N-n-propylnorapomorphine and R-(-)-apomorphine displayed a comparable oral bioavailability (1%), while the mono-hydroxy analog R-(-)-11-hydroxy-N-n-propylnoraporphine displayed a slightly higher oral bioavailability (3%). In conclusion, R-(-)-N-n-propylnorapomorphine and R-(-)-11-hydroxy-N-n-propylnoraporphine did not show a substantial improvement in bioavailability. However, due to the clear difference in their efficacy in decreasing dopamine release, in spite of the similar agonist binding affinities to the dopamine D(2) receptor of the two analogs compared to R-(-)-apomorphine, they could be useful alternatives for apomorphine in the treatment of Parkinsons disease.