A comparison between the dynamics of horizontal and vertical axis offshore floating wind turbines.

The need to further exploit offshore wind resources in deeper waters has led to a re-emerging interest in vertical axis wind turbines (VAWTs) for floating foundation applications. However, there has been little effort to systematically compare VAWTs to the more conventional horizontal axis wind turbine (HAWT). This article initiates this comparison based on prime principles, focusing on the turbine aerodynamic forces and their impact on the floating wind turbine static and dynamic responses. VAWTs generate substantially different aerodynamic forces on the support structure, in particular, a potentially lower inclining moment and a substantially higher torque than HAWTs. Considering the static stability requirements, the advantages of a lower inclining moment, a lower wind turbine mass and a lower centre of gravity are illustrated, all of which are exploitable to have a less costly support structure. Floating VAWTs experience increased motion in the frequency range surrounding the turbine [number of blades]×[rotational speed] frequency. For very large VAWTs with slower rotational speeds, this frequency range may significantly overlap with the range of wave excitation forces. Quantitative considerations are undertaken comparing the reference NREL 5 MW HAWT with the NOVA 5 MW VAWT.

Vitamin A deficiency induces motor impairments and striatal cholinergic dysfunction in rats.

Vitamin A and its derivatives, retinoids, are involved in the regulation of gene expression by binding two nuclear receptor families, retinoic acid receptors and retinoid X receptors. Retinoid receptors are highly expressed in the striatum, revealing an involvement of this system in the control of movement as demonstrated by previous observations in knockout mice. To further assess the role of retinoids in adult striatal function, the present study investigated the effect of vitamin A deprivation on rat motor activity and coordination, the rate of synthesis and release of dopamine, the functioning of D1 and D2 receptors and their expression in the striatum. Moreover, the content of acetylcholine in the striatum was measured. Results show that 24 weeks of postnatal vitamin A deprivation induced severe locomotor deficits and impaired motor coordination. Vitamin A deprivation rats showed a significant hyperactivity following D1 receptor stimulation by R(+)-6-chloro-7,8-dihydroxy-1-phenyil-2,3,4,5-tetrahydro-1H-3-benzazepine or amphetamine and reduced catalepsy in response to haloperidol treatment. This different response to the above drugs is not due to a change in striatal DA release or synthesis between vitamin A deprivation and control animals. In situ hybridization experiments showed identical level of expression for the D1 and D2 receptor transcripts. On the other hand, the striatal tissue content of acetylcholine was reduced significantly by about 30% starting from the initial manifestation of motor deficits. We suggest that the locomotor impairment could be imputable to the dysfunction in striatal cholinergic interneurons. Our results stress the basic role of vitamin A in the maintenance of basal ganglia motor function in the adult rat brain.

Augmented cocaine-induced accumbal dopamine efflux, motor activity and place preference in rats fed with a tryptophan-deficient diet.

In the present study we demonstrate that consumption of a tryptophan-deficient diet for a period of 14 days decreased the striatal serotonin and 5-hydroxyindolacetic acid tissue content in rats, whereas the level of dopamine remained unchanged. Under this condition of diminished serotonergic tone, a challenge dose of cocaine (10mg/kg, i.p.) significantly increased motor activity and dopamine extracellular content in the nucleus accumbens compared to rats fed with a balanced diet. We moreover found that pretreatment with cocaine (7 and 10mg/kg, i.p.) produced a significant increase in preference for a cocaine-associated environment in the tryptophan-deficient group compared to control rats. Our experiments show that a low tone of serotonergic system, augments the behavioural reinforcing effect of cocaine and that this effect may be due to a increased cocaine-induced accumbal dopamine release. These data indicate that a tryptophan-deficient diet alters the behavioural and neurochemical effect of psychostimulants, such as cocaine, and suggest an important role of serotonin in modulation of these effects.

Cell growth and cholesterol metabolism in human glucose-6-phosphate dehydrogenase deficient lymphomononuclear cells.

Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose-monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD-normal (n = 5) and -deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]-thymidine incorporation) cholesterol synthesis and esterification ([14C]-acetate and [14C]-oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT-PCR) all increased following lectin stimulation in both normal and G6PD-deficient cells. However, these parameters were significantly lower in G6PD-deficient cells (P < 0.05). It is of interest that G6PD-deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD-deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.

Early exposure to restraint stress enhances chemical carcinogenesis in rat liver.

This study examines the effect of a stress-associated condition on chemical hepatocarcinogenesis in the rat. Rats were given diethylnitrosamine (200 mg/kg. b.w., i.p.), followed, 1 week later, by three cycles of immobilization at room temperature. Two weeks after the last cycle they were treated according to the resistant hepatocyte protocol. At 4 weeks after selection, mean size of glutathione-S-transferase 7-7 positive foci/nodules was increased in the immobilized group (0.82+/-0.22 vs. 0.25+/-0.04 mm(2) in controls). Furthermore, at the end of 1 year 10/13 animals (77%) developed hepatocellular carcinoma in the former group, while only 6/14 (43%) incidence of cancer was found in controls. These results indicate that exposure to restraint stress early during carcinogenesis enhances the development of chemically-induced hepatocellular carcinoma in the rat.

Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390.

The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1-D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were antagonized not only by the selective D2 antagonist sulpiride but, unexpectedly, also by the selective D1 antagonist SCH 23390. The results suggest that DA receptors mediating the yawning response are of the D2 type, and that these receptors are connected with D1 receptors in such a way that the blockade of the latter results in the functional inactivation of the former.

Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area.

In unanesthetized rats the intravenous administration of low doses of ethanol (0.125-0.5 g/kg) produced a dose-dependent increase (30-80%) in the firing rate of dopaminergic (DA) neurons in the Ventral Tegmental Area (VTA). In agreement with previous observations, a dose range between 0.5 and 2 g/mg of ethanol was needed to produce comparable stimulant responses in DA neurons of the Substantia Nigra Pars Compacta. However, in anesthetized rats, doses of ethanol up to 1 g/kg failed to activate VTA-DA neurons. The high sensitivity of VTA-DA neurons to ethanol activation suggests that they might be involved in the reinforcing properties of the drug.

Possible role of dopamine D1 receptor in the behavioural supersensitivity to dopamine agonists induced by chronic treatment with antidepressants.

The effect of chronic treatment with antidepressants (ADs) on the behavioral responses to LY 171555, a selective D2 receptor agonist, SKF 38393, a selective D1 receptor agonist, and B-HT 920, a selective DA autoreceptor agonist, was studied in rats. In normal rats small, intermediate and high doses of LY 171555 produced hypomotility, hyperactivity and stereotypies, respectively. Chronic but not acute pretreatment with imipramine (IMI) greatly potentiated the motor stimulant effect of LY 171555, but failed to modify its stereotypic and sedative effect. The potentiation of the motor stimulant effect of LY 171555 was observed also after chronic, but not acute, treatment with desmethylimipramine (DMI), mianserin (MIA) or repeated electroconvulsive shock (ECS). Chronic treatment with IMI failed to modify the effect of SKF 38393 (motor stimulation, grooming and penile erection), but reversed the sedative effect of B-HT 920 into a motor stimulant response. The motor stimulant response to LY 171555 in IMI-pretreated animals was suppressed by L-sulpiride, a D2 antagonist, and by a combination of reserpine with alpha-methyltyrosine (alpha-MT), but it was only partially antagonized by high doses of SCH 23390, a selective D1 antagonist. The results indicate that chronic treatment with ADs potentiates the behavioural responses mediated by the stimulation of postsynaptic D2 receptors in the mesolimbic system and suggest that this behavioural supersensitivity is due to enhanced neurotransmission at the D1 receptor level.

Dopamine receptors mediating yawning: are they autoreceptors?

Yawning was induced in rats by the (+) enantiomer of 3PPP, while (-)-3PPP was inactive. Yawning was present 24, but not 1, 6 and 12 h after reserpine treatment. The (+)-3PPP-induced yawning was antagonized by haloperidol and sulpiride but not by domperidone. Reserpine-induced yawning was antagonized by sulpiride and by alpha-methyltyrosine suggesting that this behavior may be induced by endogenously released dopamine. Reserpine-pretreatment potentiated (+)-3PPP-induced yawning. The results argue against the view that yawning is the behavioural correlate of autoreceptor-mediated inhibition of DA transmission, and suggest that this behaviour is due to the stimulation of a special population of central postsynaptic DA receptors.

Estrogens antagonize apomorphine-induced yawning in rats.

The administration of a small dose of apomorphine (50 micrograms/kg s.c.) induced repeated episodes of yawning in male rats. Short-term (3 days) treatment with 17 beta-estradiol antagonized apomorphine-induced yawning in male rats. Moreover, apomorphine induced yawning much less effectively in female than in male rats. These results suggest that both endogenous or exogenously administered estrogens induce subsensitivity of the DA receptors mediating yawning in rats.

Behavioural sensitization of mesolimbic dopamine D2 receptors in chronic fluoxetine-treated rats.

A common action of chronic antidepressant treatments is the potentiation of dopaminergic transmission in the limbic system. We now report that chronic, but not acute, treatment with fluoxetine (2.5 mg/kg by intragastric gavage once a day for 21 days) potentiates the locomotor stimulant effect of quinpirole, a selective dopamine D2/D3 receptor agonist. However, neither quinpirole-induced stereotypies nor the sedative effects elicited by low doses of this dopamine receptor agonist are influenced by chronic fluoxetine. These results suggest that fluoxetine, as well as classical antidepressants, sensitize postsynaptic dopamine D2/D3 receptors in the mesolimbic system.

SCH 23390, a selective dopamine D1 antagonist, activates dopamine neurons but fails to prevent their inhibition by apomorphine.

SCH 23390, a rather selective D1 receptor blocker, activates the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons) in rats, similarly to haloperidol (a D1-D2 receptor antagonist) and sulpiride (a selective D2 receptor blocker). These neuroleptics produce no additional increase over the maximal activation produced by SCH 23390. Unlike haloperidol or sulpiride, SCH 23390 fails to prevent the inhibition by apomorphine of SN-DA neurons, a DA autoreceptor-mediated effect. It is suggested that the doses of SCH 23390 that stimulate DA neurons block D2 in addition to D1 receptors, or that D1 blockade results in the functional inactivation of a specific population of D2 receptors as well. The failure of SCH 23390 to block the apomorphine effect indicates that DA autoreceptors can be pharmacologically differentiated form postsynaptic DA receptors.

Haloperidol-induced vacuous chewing in rats: suppression by alpha-methyl-tyrosine.

Chronic treatment of rats with haloperidol (1 mg/kg twice daily for 4 weeks) induced repetitive vacuous chewing movements (VC), that persisted for over 72 h after haloperidol withdrawal. Haloperidol-induced VC were inhibited by the s.c. administration of the specific dopamine D1, receptor antagonist, SCH 23390 (0.025-0.100 mg/kg), in a dose-dependent manner, and were totally suppressed by an acute challenge with haloperidol (2 mg/kg i.p.) and by the dopamine synthesis inhibitor, alpha-methyl-tyrosine (AMT) (200 mg/kg i.p.). In AMT-treated rats, VC were reinstated by the administration of the selective D1 agonist, SKF 38393. The results support the hypothesis that chronic haloperidol-induced VC are mediated by dopamine acting selectively upon D1 receptors.

Dizocilpine prevents the enhanced locomotor response to quinpirole induced by repeated electroconvulsive shock.

Repeated administration of electroconvulsive shock, as expected, potentiated the locomotor stimulant response to quinpirole (0.3 mg/kg s.c.), a dopamine D2-like receptor agonist. Chronic, but not acute, treatment with the NMDA receptor non-competitive antagonist dizocilpine (0.3 mg/kg i.p.) prevented electroconvulsive shock-induced potentiation of quinpirole locomotor response. These results suggest that NMDA receptor activation is necessary for the development of supersensitivity to dopamine receptor agonists produced by repeated electroconvulsive shock. The relevance of this observation in regard to the mechanism of electroconvulsive shock therapeutic effect is discussed.

Chronic lithium chloride fails to prevent imipramine-induced sensitization to the dopamine D(2)-like receptor agonist quinpirole.

Lithium salts, an effective antimanic treatment, are able to prevent the development of the dopaminergic behavioural supersensitivity induced by chronic treatment with neuroleptics, by denervation of the dopaminergic terminal fields and by rapid eye movements (REM) sleep deprivation, which is considered a model of mania. We have studied the effect of a lithium (LiCl) diet, inducing a lithium serum level in the range of therapeutic efficacy, on the development of the supersensitivity to the locomotor effect of the dopamine D(2)-like receptor agonist, quinpirole, induced by chronic treatment with the antidepressant drug, imipramine. The results show that lithium is not able to prevent the development of such behavioural supersensitivity. The present data suggest that antidepressant-induced dopaminergic supersensitivity might provide a useful model of those manic states induced by (or subsequent to) antidepressant treatments. Moreover, the finding is consistent with the view that antidepressant-induced dopaminergic supersensitivity might play a role in the therapeutic effect of these drugs (which is known to be augmented by lithium, and not antagonised). Finally, the results show that the dopaminergic supersensitivity induced by imipramine is qualitatively different from that induced by neuroleptics or denervation of the dopaminergic terminal fields.

The role of dopamine in the mechanism of action of antidepressant drugs.

The present paper reviews evidence on the effect of antidepressant treatments on dopamine transmission. Chronic treatment with antidepressant drugs potentiates the behavioural stimulant responses elicited by the stimulation of dopamine receptors, including reward-related behaviours. Moreover, antidepressants affect dopamine release in several brain areas. The reviewed literature is discussed in terms of the possible mechanisms underlying antidepressant-induced supersensitivity to dopamine-mediated behavioural responses, and of the possible implications for the therapeutic effect of these drugs. It is concluded that the potentiation of dopaminergic neurotransmission induced by chronic antidepressant treatments might contribute to their therapeutic effect.

The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin inhibits male copulatory behaviour in rats.

The effect of an intracerebroventricular (i.c.v.) injection of the oxytocin antagonist, d(CH2)5Tyr(Me)-Orn8-vasotocin, on the copulatory behaviour of vigorous male rats in the presence of females in estrus was studied. The peptide (2.5, 25 and 50 ng, 15 min before mating tests) decreased the number of mounts and intromissions, and abolished ejaculation almost completely at all doses tested. The peptide failed to significantly influence motor activity at the doses used. The results support the hypothesis that central oxytocin plays a physiological role in the expression of copulatory behaviour.

Sedation and sleep induced by high doses of apomorphine after blockade of D-1 receptors by SCH 23390.

The effect of SCH 23390, a selective blocker of D-1 receptors, on apomorphine-induced behavioural and EEG changes was studied in rats. In control rats, a low dose of apomorphine (50 micrograms/kg s.c.) produced sedation associated with EEG synchronization. A high dose of apomorphine (1 mg/kg s.c.) produced stereotypy associated with EEG desynchronization. At the dose of 1 mg/kg i.p., SCH 23390 decreased motor activity but failed to alter the EEG pattern. The administration of either the low or high dose of apomorphine to SCH 23390-treated rats elicited a marked sedative response associated with EEG synchronization. The EEG synchronization produced by apomorphine (50 micrograms/kg) in SCH 23390-treated rats was prevented by (-)-sulpiride (25 mg/kg i.p.), a D-2 receptor blocker. It is concluded that by preventing the excitatory response to apomorphine SCH 23390 discloses the existence of a population of D-2 receptors mediating sedation and sleep.

Stress-induced insomnia: opioid-dopamine interactions.

REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour.

Chronic administration of l-sulpiride at low doses reduces A10 but not A9 somatodentritic dopamine autoreceptor sensitivity.

The effect of chronic treatment (twice daily for 21 days) with low doses of l-sulpiride (2 mg/kg i.p.) on the apomorphine-induced inhibition of A10 and A9 dopaminergic neurons was compared with the effect of chronic administration of the classic antidepressant desipramine (20 mg/kg i.p. daily for 21 days). Intravenous administration of apomorphine (0.01-0.04 mg/kg), to rats treated chronically with l-sulpiride, produced a reduction of the spontaneous firing rate of A9 dopaminergic neurons not significantly different from that observed in control (saline-treated) rats. In contrast, apomorphine at the same doses was more potent in inhibiting A10 firing in control rats than in l-sulpiride-treated subjects. On the other hand, desipramine-treated rats were found normosensitive (as compared to saline-treated rats) to the inhibitory properties of apomorphine in both A9 and A10 dopaminergic neurons. It is suggested that chronic l-sulpiride-induced reduction of autoreceptor sensitivity in the A10 region may contribute to its clinical antidepressant effect.