Aspects of tic like behaviour and serotonergic control

Tic-like movements in rodents bear close similarities to those observed in humans both pharmacologically and morphologically. Pharmacologically, tics are modulated by serotonergic and dopaminergic systems and abnormalities of these systems have been reported in Tourette's Syndrome (TS). Therefore, serotonergic and dopaminergic modulation of tics induced by a thyrotrophin-releasing hormone (TRH) analogue were studied as possible models for TS. The TRH analogue MK771 induced a variety of tic like movements in mice; blinking fore-paw-licking and fore-paw-tremor were quantified and serotonergic and dopaminergic modulation was investigated. The selective dopamine D1 receptor antagonists SCH23390 and SCH39166 and dopamine D2 antagonists raclopride and sulpiride had no effect on MK771 induced blinking. The D1 antagonists attenuated fore-paw-tremor and -licking while the D2 antagonists were generally without effect on these behaviours. Ketanserin (5-HT2A/ alpha-1 antagonist) and ritanserin (5-HT2A/2C antagonist) were able to attenuate MK771-induced blinking and ketanserin, mianserin (5-HT2A/2C antagonist) and prazosin (alpha-1 adrenoceptor antagonist) were able to attenuate MK771-induced fore-paw-tremor and -licking. The 5-HT2C/2B antagonist SB200646A was without effect on blinking and fore-paw-licking but dose-dependently potentiated fore-paw-tremor. The 5-HT1A agonists 8-OH DPAT and buspirone attenuated blinking at the lower doses tested but were ineffective at the higher doses; the converse was found for fore-paw-licking and -tremor behaviours.The effects of these ligands appeared to be at a postsynaptic 5-HTlA site since para-chlorophenylalanine was without effect on the manipulation of these behaviours. (S)-W A Y100135 was without effect on MK771-induced behaviours, spontaneous and DOl-induced head shakes. Because kynurenine potentiates head shakes and plasma concentrations are raised in TS patients the effects of kynurenine on the 5-HT2A/2C agonist DOl mediated head shake were established. Kynurenine potentiated the DOl head shake. Attempts were made to correlate serotonergic unit activity with tic like behaviour in cats but this proved unsuccessful. However, the pharmacological understanding of 5-HTlA receptor function has been hampered because of the lack of selective antagonists for this site. For this reason the effects of the novel 5-HTlA antagonists (S)-WA Y- 100135 and WAY -100635 were tested on 5-HT single-unit activity recorded from the dorsal-raphe-nucleus in the behaving cat. Both drugs antagonised the suppression of unit activity caused by 8-0H DPAT. (S)-WA Y-100135 reduced unit activity whereas WAY-100635 increased it. This suggests that WAY-100635 is acting as an antagonist at the 5-HTlA somatodendritic autoreceptor and that (S)W A Y -100135 acts as a partial agonist at this site. Aspects of tic like behaviour and serotonergic control are discussed.

Drug action on anxiety models with special reference to serotonergic mechanisms

A study has been made of drugs acting at 5-HT receptors on animal models of anxiety. An elevated X-maze was used as a model of anxiety for rats and the actions of various ligands for the 5-HT receptor, and its subtypes, were examined in this model. 5-HT agonists, with varying affinities for the 5-HT receptor subtypes, were demonstrated to have anxiogenic-like activity. The 5-HT2 receptor antagonists ritanserin and ketanserin exhibited an anxiolytic-like profile. The new putatuve anxiolytics ipsapirone and buspirone, which are believed to be selective for 5-HT1 receptors, were also examined. The former had an anxiolytic profile whilst the latter was without effect. Antagonism studies showed the anxiogenic response to 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT) to be antagonised by ipsapirone, pindolol, alprenolol and para-chlorophenylalanine, but not by diazepam, ritanserin, metoprolol, ICI118,551 or buspirone. To confirm some of the results obtained in the elevated X-maze the Social Interaction Test of anxiety was used. Results in this test mirrored the effects seen with the 5-HT agonists, ipsapirone and pindolol, whilst the 5-HT2 receptor antagonists were without effect. Studies using operant conflict models of anxiety produced marginal and varying results which appear to be in agreement with recent criticisms of such models. Finally, lesions of the dorsal raphe nucleus (DRN) were performed in order to investigate the mechanisms involved in the production of the anxiogenic response to 8-OH-DPAT. Overall the results lend support to the involvement of 5-HT, and more precisely 5-HT1, receptors in the manifestation of anxiety in such animal models.

Effects of some 5-hydroxytryptamine and related ligands in anxiety models

Drugs acting at 5-HT receptors were evaluated on three animal models of anxiety. On the elevated X-maze test the majority of 5-HT1 agonists were found to be anxiogenic. However, ipsapirone was anxiolytic and buspirone and gepirone were inactive. The 5-HT2 agonist DOI and the 5-HT2 antagonist ritanserin were anxiolytic while ICI 169,369, a 5-HT2 antagonist was inactive. All 5-HT3 antagonists tested were inactive in this test, while the indirect serotomimetics zimeldine and fenfluramine were anxiogenic. Neither beta-adrenoceptor agonists nor antagonists had reproducible effects on anxiety in this model. Combined beta-1/beta-2 adrenoceptor antagonists reversed the anxiogenic effects of 8-OH-DPAT while selective beta-1 or beta-2 antagonists did not. On the social interaction model the 5-HT1 agonists 8-OH-DPAT, RU 24969 and 5-MeODMT were anxiogenic and ipsapirone was anxiolytic. The 5-HT2 agonist DOI and the beta-adrenoceptor- and 5-HT- antagonist pindolol were anxiolytic, while the 5-HT2 and 5-HT3 antagonists were inactive. In the marble burying test, the 5-HT upake inhibitors zimeldine, fluvoxamine, indalpine and citalopram, the 5-HT1B/5-HT1C agonists mCPP and TFMPP and the 5-HT2/5-HT1C agonist DOI reduced marble burying without affecting locomotor activity. 5-HT1A agonists and the 5-HT2 and 5-HT3 antagonists were without effect. Lesions of the dorsal raphe nucleus reversed the anxiogenic effects of 8-OH-DPAT in the X-maze model. The implication of these results for the understanding of the pharmacology of 5-HT in anxiety is discussed.

Effect of processing on sulphur antioxidants in polyolefins

The effect of processing on the antioxidant activity of sulphur-containing compounds, with particular reference to nickel dialkyldithiophosphates and their corresponding di sulphides, were studied in polyolefins under melt, thermal and photo-oxidative conditions. These compounds were evaluated both at low (normal) and high (concentrates) concentrations. In general, the dithiophosphates were found to be very efficient melt stabilisers at normal concentrtion levels, and compare quite favourably with the best commercially available systems. The nickel dithiophosphates were also found to be very efficient thermal stabilisers for polyolefins, but their activity is highly dependent on the alkyl substituent in the molecule. The corresponding disulphides on the other hand showed very little activity under thermal oxidative conditions, and this was attributed to their inefficiency in scavenging alkyl peroxyl radicals since both compounds possess similar peroxidolytic activity. Furthermore, the nickel dithiophosphates were found to be excellent photo stabilisers for mildly-processed polyolefins while the corresponding disulphides only offer slight protection to the polymer. Oxidative processing of the disulphide, however, results in a dramatic improvement in their photo antioxidant activity. Thionophospho-ric acid, a major oxidation product of dithiophosphates, was also shown to have photo antioxidant activity similar to that of the disulphides. A combination of a U.V. absorber with the nickel complex and/or the disulphide resulted in a synergistic stabiliser system which was further augmented by oxidative processing. Moreover, the dilute analogues of such multicomponent stabiliser concentrates also showed excellent melt, thermal and photo-stabilising activity. The mechanistic studies carried out on the nickel complex and the corresponding disulphide clearly identified the thionophosphoric acid a a major transformation product although various triesters were formed as reaction intermediates. The mechanisms of the antioxidant action of the dithiophosphates, which is believed to involve a cyclical process similar to that shown for simple alkyl sulphides and nitroxyls, are discussed.

Injection locking-based pump recovery for phase-sensitive amplified links

An injection locking-based pump recovery system for phase-sensitive amplified links, capable of handling 40 dB effective span loss, is demonstrated. Measurements with 10 GBd DQPSK signals show penalty-free recovery of a pump wave, phase modulated with two sinusoidal RF-tones at 0.1 GHz and 0.3 GHz, with 64 dB amplification. The operating power limit for the pump recovery system is experimentally investigated and is governed by the noise transfer and phase modulation transfer characteristics of the injection-locked laser. The corresponding link penalties are explained and quantified. This system enables, for the first time, WDM compatible phase-sensitive amplified links over significant lengths. © 2013 Optical Society of America.

Optical injection-locking-based pump recovery for phase-sensitively amplified links

An injection-locking-based pump recovery system for phase-sensitively amplified links is proposed and studied experimentally. Measurements with 10 Gbaud DQPSK signals show penalty-free recovery of 0.8 GHz FWHM bandwidth pump with 63 dB overall amplification. © 2012 OSA.

Discrete solitons in coupled active lasing cavities

We examine the existence and stability of discrete spatial solitons in coupled nonlinear lasing cavities (waveguide resonators), addressing the case of active defocusing media, where the gain exceeds damping in the low-amplitude limit. A new family of stable localized structures is found: these are bright and gray cavity solitons representing the connections between homogeneous and inhomogeneous states. Solitons of this type can be controlled by discrete diffraction and are stable when the bistability of homogenous states is absent. © 2012 Optical Society of America.

Cardiocentric neurophysiology:the persistence of a delusion

Aristotle is well known to have taught that the brain was a mere coolant apparatus for overheated blood and to have located the hegemonikon in the heart. This teaching was hotly disputed by his immediate successors in the Alexandrian Museum, who showed that the brain played the central role in psychophysiology. This was accepted and developed by the last great biomedical figure of classical antiquity - Claudius Galen. However, Aristotle's cardiocentric theory did not entirely disappear and this article traces its influence through the Arabic physicians of the Islamic ascendancy, into the European Middle Ages where Albertus Magnus' attempt to reconcile cardiocentric and cerebrocentric physiology was particularly influential. It shows how cardiocentricity was sufficiently accepted to attract the attention of, and require refutation by, many of the great names of the Renaissance, including Vesalius, Fernel, and Descartes, and was still taken seriously by luminaries such as William Harvey in the mid-seventeenth century. The article, in rehearsing this history, shows the difficulty of separating the first-person perspective of introspective psychology and the third-person perspective of natural science. It also outlines an interesting case of conflict between philosophy and physiology. © 2013 Copyright Taylor & Francis Group, LLC.

An international cohort comparison of size effects on job growth

The contribution of different-sized businesses to job creation continues to attract policymakers’ attention; however, it has recently been recognised that conclusions about size were confounded with the effect of age. We probe the role of size, controlling for age, by comparing the cohorts of firms born in 1998 over their first decade of life, using variation across half a dozen northern European countries Austria, Finland, Germany, Norway, Sweden and the UK to pin down size effects. We find that a very small proportion of the smallest firms play a crucial role in accounting for cross-country differences in job growth. A closer analysis reveals that the initial size distribution and survival rates do not seem to explain job growth differences between countries, rather it is a small number of rapidly growing firms that are driving this result.

Beginnings : ventricular psychology

From Platonic and Galenic roots, the first well developed ventricular theory of brain function is due to Bishop Nemesius, fourth century C.E. Although more interested in the Christian concept of soul, St. Augustine, too addressed the question of the location of the soul, a problem that has endured in various guises to the present day. Other notable contributions to ventricular psychology are the ninth century C.E. Arabic writer, Qusta ibn Lūqā, and an early European medical text written by the twelfth century C.E. author, Nicolai the Physician. By the time of Albertus Magnus, so-called medieval cell doctrine was a well-developed model of brain function. By the sixteenth century, Vesalius no longer understands the ventricles to be imaginary cavities designed to provide a physical basis for faculty psychology but as fluid-filled spaces in the brain whose function is yet to be determined

Brain, mind and consciousness in the history of neuroscience

From Platonic and Galenic roots, the first well developed ventricular theory of brain function is due to Bishop Nemesius, fourth century C.E. Although more interested in the Christian concept of soul, St. Augustine, too addressed the question of the location of the soul, a problem that has endured in various guises to the present day. Other notable contributions to ventricular psychology are the ninth century C.E. Arabic writer, Qusta ibn Lūqā, and an early European medical text written by the twelfth century C.E. author, Nicolai the Physician. By the time of Albertus Magnus, so-called medieval cell doctrine was a well-developed model of brain function. By the sixteenth century, Vesalius no longer understands the ventricles to be imaginary cavities designed to provide a physical basis for faculty psychology but as fluid-filled spaces in the brain whose function is yet to be determined

Strongly localized moving discrete dissipative breather-solitons in Kerr nonlinear media supported by intrinsic gain

We investigate the mobility of nonlinear localized modes in a generalized discrete Ginzburg-Landau-type model, describing a one-dimensional waveguide array in an active Kerr medium with intrinsic, saturable gain and damping. It is shown that exponentially localized, traveling discrete dissipative breather-solitons may exist as stable attractors supported only by intrinsic properties of the medium, i.e., in the absence of any external field or symmetry-breaking perturbations. Through an interplay by the gain and damping effects, the moving soliton may overcome the Peierls-Nabarro barrier, present in the corresponding conservative system, by self-induced time-periodic oscillations of its power (norm) and energy (Hamiltonian), yielding exponential decays to zero with different rates in the forward and backward directions. In certain parameter windows, bistability appears between fast modes with small oscillations and slower, large-oscillation modes. The velocities and the oscillation periods are typically related by lattice commensurability and exhibit period-doubling bifurcations to chaotically "walking" modes under parameter variations. If the model is augmented by intersite Kerr nonlinearity, thereby reducing the Peierls-Nabarro barrier of the conservative system, the existence regime for moving solitons increases considerably, and a richer scenario appears including Hopf bifurcations to incommensurately moving solutions and phase-locking intervals. Stable moving breathers also survive in the presence of weak disorder. © 2014 American Physical Society.

Subliminal influence on generosity

We experimentally subliminally prime subjects prior to charity donation decisions by showing words that have connotations of pro-social values for a very brief time (17ms). Our main fnding is that, compared to a baseline condition, the pro-social prime increases donations by approximately 10-17 percent among subjects with strong pro-social preferences (universalism values). We find a similar effect when interacting the prime with the Big 5 personality characteristic of agreeableness. We furthermore introduce a novel method for testing for priming, "subliminity". This method reveals that some subjects are capable of recognizing prime words, and the overall results are weaker when we control for this capacity.