Publications

Preface

The dry, seemingly arid, region around Almería (the environs of Mojácar), famous or notorious (depending on one's current taste in movie-genre) for its Serge Leone 'spagetti-westerns' and by repute afflicted by long-term periods of drought, appears to invoke some catalytic chemical cascade (perhaps like the tadpole's thyroxin) that triggers the synchronous atmospheric, mountain-craig landscape and sea breezes to orchestra a concaphony of climactic convolutions resulting in dramatic lightning and thunderstorms and heavy rainfall with the fluid inundation that results, seemingly overnight, in explosions of growth and greenery. Such was the intrinsic circumstance 'in the offing' as we approached Mojácar via the "Levant-highway" bringing us from Madrid around three, a.m., in the early October morning and we responded predictably with an immediate and uncanny awareness of the converging and pending events. Was our special Indalo friend setting the stage? Certainly, this arrival was an explicit and auspicious greeting to the intrepid, yet nervous, explorers of neuroscientific phenomena and brain events. In the hour following hotel room allocation (despite the hour or place) it remained an undeniable and exquisite mark of civilised behaviour for one to exploit the 'fullfrontal' grandstand of one's balcony (glass of Spanish brandy in hand, for no matter what the hour our delightful hosts of the Parador de Mojácar will improvise - that uniquely cosmopolitan but particularly Spanish virtue) to become lost (yes, a bit like the famous "stranger-in-paradise") in the unfolding drama of lightning flashes, convulsions of thunder-lightning crashes-flashes and the sweeping fury of a full-fledged western Mediterranean downpour. These confrontations and conflagrations of nature's titan-actors, the physical elements on the distant sea-horizon, away towards the coastline of Marocco and the Pillars of Hercules, slugged it out with all the intractable and implacable Guadalcanal 'battlewagon' force and power of now-legendary "Washington" and "South Dakota", and illustrated by momentously, shockingly sudden eruptive illuminations of the recently sleeping horizon. What a welcome! The Indalo indeed loves us! The meeting will enjoy success! Some rituals may well be harmful and destructive but paradoxically the quiet, placid and benevolent rituals generally in evidence all around this lovely garden of andalusia (once the 'milch-cow' of the megaglutton Jean-Marie Soult) have offered us an exquisitely sophisticated form of civilisation. In the invigoration and excitement of 'that hour' where a wonderful and inviolate peace-of-spirit descended on the 'seizures-of-birth' of the current "Mojácar meeting", was initiated and launched the latest endeavour , the Interactive Monoaminergic Basis of Brain Disorders , held at the Parador de Mojácar, 8-12 October, 1997, and without even recourse to any form of intoxicate or sacrificial offering, so necessary to the spirituality of the ancients, all the omens were propitious.

The interactive monoaminergic bases of anxiety and depression, substance abuse disorders, schizopsychotic and movement disorders extended from serotonergic-HPA axis-adrenergic dissynchronies, nervous-immune system cul-de-sacs and labyrinths, dopamine-glutamatergic cum GABAergic cum serotonergic-nicotinic-opiate imbalances, the plethora of amphetamine-like or similar-acting stimulant-hallucinogenic 'rave-party' sensation drugs and their neurotoxicological penchances, the definition and validation of the fashionable animal models by cross-validations and refutations of clinical syndromes in schizophrenia, the clinical/preclinical empirical models of psychiatry and their brain image analyses of neurodevelopmental structural malformations, the complicated cognitive disturbances inherent to the negative symptoms with perverted, diverted and subverted second messenger cascades, the unbalanced symphony of dopamine subreceptor contingents that induce a bedlam of breakdown and confusion in the monoaminergic orchestration, to the present-day status of putative synergistic equations that may resurrect current levodopa therapy in those surviving nigrostriatal dopamine neurons and the available and forthcoming chemical entities to ensure the longevity of those neurons and others from both convergent and divergent pathways. Alas, the perfect balance we determinedly sought between preclinical and clinical studies fell disappointingly short of the mark with a somewhat overwhelming preponderance of the laboratory analyses. Despite this, the overall purpose of examination and description of the interactive processes between monoaminergic pathways that determine behavioural expressions and the clinical outcomes of therapeutic compounds pertaining to anxiety, depression and problems of affect, drug abuse, tolerance and dependence, drug ameliorations of respectively negative and positive symptoms and special requirements of validated and acceptable therapeutic agents, the exciting breakthroughs in treatments of epilepsy, parkinsonism and related disorders of movement and cognition that originate from the elusive principles of synergism and serendipity, was achieved to the extent that synopses of the components of the meeting signalled an impressive substrate. The present volume discusses possible, nay plausible, disease causation, the neurochemical/anatomical background and the mechanisms of action of psychotropic drugs with the disease states under scrutiny. It has been edited conscientiously to ensure utility and unambiguity to psychiatrists, pharmacologists, neurologists and all other neuroscientists.

We live in an age when minor, significant or catastrophic discoveries of brain abnormalities or insufficiencies proliferate with discomforting, perhaps even frighteningly accumulative, regularity: our self-imposed directive is to apply all the means at our disposal (whether single or collective) to obviate, obstruct or oppose these cerebral misadventures and maladies. During the pre- and postmeeting periods two of us were discovered to possess structural problems of our brain, one benign, the other congenital. In the operative aftermath, with a half-year plus perspective one may acknowledge, once again, the vicarious Indalo mediation. The meeting, this volume and all succeeding enterprises comprehend a magnified, multi-faceted and multitudinous intellectual environment with sincere thanksgiving of the munificent benevolence, from wherever it originated. Alas, such good fortune remains disconcertingly and alarmingly selective: the volume is dedicated to José Carlos Barnabé , a highly promising young Brazilian neuroscientist involved in projects to improve the nutritive circumstance of a large portion his poverty-striken countryfolk, just completing a PhD thesis at the department of Neurobiology, University of Riberao Preto, Brazil, and a research associateship at Joe Huston's lab in Dusseldorf. Quite recently, he became father to a now two-year old son: around the time (1996) of Daniel's birth, José travelled home to a long-delayed sojourn with his parents and brothers and one morning suffered what appeared a seizure and some hours later fell into a coma from which he has not yet emerged, to regain full consciousness. Many emotions erupt: sorrow, bewilderment, frustration at the wastage, unfairness, helpless anger, and not least of all fear-for-self and, naturally, these are all understandable as José was a character Shakespeare has described in different forms upon the prevailing theme of honesty, humility and nobility of personality whose unrestricted loyalty one of us experienced in "the nick of time". All of us that observe, assimilate and ruminate the lessons, idiosyncrasies and restrictions of the Interactive Monoaminergic Basis of Brain Disorders will pray for, contemplate and extend our thoughts towards that young brain wherever it may be on its celestial journey into a different level of awareness that we presently lack sufficient understanding and skill at awakening.

One recurring bonus of a scientific meeting cosseted within the Mojácar environment is the introducing, reinforcing and consolidating of friendships and acquaintances, discoveries of hidden or not-so-evident personal qualities, the spontaneous occurrence of humorous incidents and/or harmless misadventures the telling of which may vary from the amusing-anecdotal to the vicinity of Sunday-tabloid-lawsuit dilemma. Naturally, at the beginning of a meeting, such as this, the extent of emotional fear and phobic anxiety may easily be assessed at the latter dimension and with each consummated progression from Speaker-to-Speaker, session-to-session and day-to-day advance the mood approaches (if one has been good to one's pet Indalo in the closet, that is) the former dimension. Under conditions of extreme good fortune (as we experienced it), 'the chalice of bonhomie runneth over'. As previously indicated, exquisite cuisine, Spanish wine and mellow, congenial company do go a long way to the foundation of that bonhomie (for one of us the relating of stories apocryphal to legendary and inimitable Sir Winston Churchill invariably goes a very long way!). The present constellation of speakers and participants provided all the necessary ingredients to this happy drama. One of the finest salutations an organising body can extend the Invited Speakers of a scientific meeting is the epithet that they performed a highly professional job, were distinguished in their punctuality, offered good-humoured and stoic company, laughed at all our jokes and slip-ups, and, never ever complained; "if one ever takes up wearing a hat, one shall take it off to them, retrospectively". In the present circumstance, an additional indication of our speakers' superlative conduct was the 'presentation-manuscript compliance measure' by which the seemingly impossible was achieved: every single speaker submitted his/her book chapter. Even if we never achieve this performance again – it's a wonderful experience. One Invited Speaker was put-on-the-spot. The task of the after-dinner speaker is always unenviable, never extended its fair share of appreciation and invariably bedevilled by logistic and spontaneous irritants (e.g. the wayward behaviours of slide projectors in the dining room); therefore only a Senatus Principus of pre-Caesarian calibre should, advisedly, ever be assigned this special task. Alberto Portera-Sanchez , as on innumerable occasions before, rose to the occasion - entertaining, yet intense on his theme, knowledgeable yet witty, sympathetico and sharing of his secret insights into the neuroscience of art. Other favourites joined us to make each chapter memorable: El Manitas, Bernard , resident philosopher and sage, had prepared another parable of handicraft; this new story evincing another brain, a colour-explosive glass reincarnation of the Indalo, incorporating dopaminergic-noradrenergic-serotonergic pathways as each, in turn and collectively, is modulated by GABA, Mr. Diego Martínez in his secure, reassuring presence, Mr. José Hernández of the eagle-eye directing the titillation of the palate and satiation of the beast, and certainly far from least, the hospitable personnel of the Parador de Mojácar : In the words of a very famous and quite outstanding but distressingly anti-social actor-of-the-silverscreen - "This is as good as it ever, ever gets".

T. Archer R.J. Beninger T.Palomo