Immunological analogues of band 3, the anion transporter of the human erythrocyte, have been identified in all cells, including both isolated neurons and neurons of the central nervous system. We hypothesized that the anion channel is altered in neurological disease associated with choreiform movements because γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, binds to its receptor and opens an integral membrane chloride channel. In order to examine this hypothesis, we studied a family with a serious, progressive, genetic neurologic disorder with acanthocytosis (choreoacanthocytosis) that resembles Huntington's chorea. We selected choreoacanthocytosis because erythrocytes, which are readily obtained, are affected in this disease as well as the central nervous system. Biochemical studies of erythrocytes from the proposita, mother, and brother revealed that sulfate transport Vmax was increased, and glucose efflux was decreased. Erythrocytes exhibited immunological changes indicative of cellular aging/transporter damage. In addition, transporter reactive antibodies were present. This is the first evidence for abnormalities of membrane transport in this neurologic disorder.

The present study explored the antinociceptive effects of H3 (R-alpha-methylhistamine) and GABAB (baclofen) receptor ligands in an orofacial model of pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (50 μl, 5 %) in the upper lip region, and the number of jumps and time spent face rubbing was recorded for 40 min. Formalin produced a marked biphasic pain response; first phase, 0-10 min (jumps), and second phase, 15-40 min, (rubbing). Baclofen (50 μg) injected into the rat wiskerpad 5 min before formalin administration suppressed both phases of pain whereas R-alpha-methylhistamine (12.5 μg) abolished the first phase only. Brains were taken immediately after behavioral testing was completed. HPLC/ED analysis showed that 5-hydroxytryptamine (5-HT) turnover was increased in hippocampus, thalamus, and brain stem of all formalin groups, excepting the baclofen group in which the balance of 5-HT metabolism was restored to control values. These findings demonstrate that GABAB receptors represent peripheral targets for analgesia. Consequently, locally administered baclofen may be a useful approach in treating inflammatory trigeminal pain.

Despite the consensus that glutamatergic and GABAergic imbalance is likely to be involved in anesthesia or coma, there is little known about molecular mechanisms of action of gaseous anesthetics. The target article by Smythies (1999) is engagingly analytical and insightful, proposing novel and testable hypotheses for the molecular mechanisms of action of anesthetics as well as for processes that may be involved in coma. The most creative and convincing of his hypotheses concerns the crucial role of iron in maintaining neural respiration and energy production as well as its involvement in synaptic plasticity. Smythies' paper is certain to stimulate new ideas and experiments on the molecular mechanisms of anesthesia and coma.

The present study explored the antinociceptive effects of H3 (R-alpha-methylhistamine) and GABAB (baclofen) receptor ligands in an orofacial model of pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (50 μl, 5 %) in the upper lip region, and the number of jumps and time spent face rubbing was recorded for 40 min. Formalin produced a marked biphasic pain response; first phase, 0-10 min (jumps), and second phase, 15-40 min, (rubbing). Baclofen (50 μg) injected into the rat wiskerpad 5 min before formalin administration suppressed both phases of pain whereas R-alpha-methylhistamine (12.5 μg) abolished the first phase only. Brains were taken immediately after behavioral testing was completed. HPLC/ED analysis showed that 5-hydroxytryptamine (5-HT) turnover was increased in hippocampus, thalamus, and brain stem of all formalin groups, excepting the baclofen group in which the balance of 5-HT metabolism was restored to control values. These findings demonstrate that GABAB receptors represent peripheral targets for analgesia. Consequently, locally administered baclofen may be a useful approach in treating inflammatory trigeminal pain.

Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurode-velopmental components, demonstate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cogntive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, 'healthy' young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed.

Substance abuse is a frequent comorbid condition with other psychiatric disorders including schizophrenia and depression. These disorders may share a common substrate at the neurotransmitter or neurocircuit level. One candidate is hypofunction of the glutamate system. Several lines of evidence suggest that N-methyl-D-aspartate (NMDA) receptors may hypofunction in schizophrenia. Thus, NMDA receptor antagonists are schizophrenogenic; postmortem and imaging results point to reduced NMDA receptor function in schizophrenic brains; a number of genes that have been linked to schizophrenia code for proteins that influence NMDA function; and there is preliminary evidence that pro-NMDA drugs may be therapeutic in the treatment of schizophrenia. One of the most effective therapeutics for the treatment of substance abuse in schizophrenic people is clozapine, and clozapine may act at the glycine modulatory site to enhance NMDA receptor function. This preliminary line of evidence may link schizophrenia and drug abuse to a common neurochemical base, subnormal NMDA receptor function. People with schizophrenia and drug abusers similarly show deficits in tasks known to be sensitive to ventromedial prefrontal cortical damage, and both groups show decreased activation in the ventral striatum during reward anticipation in functional magnetic resonance imaging studies. These observations implicate common prefrontal cortical-striatal circuits and their modulation by hippocampal projections in schizophrenia and substance abuse. Withdrawal from substance abuse and depression both have been linked to changes in the function of several neurotransmitters including serotonin, dopamine and glutamate. These findings suggest possible common substrates and novel therapeutic approaches. Further studies are needed to fully characterize the neurocircuits and transmitters involved in various psychiatric disorders and their possible common elements in comorbid drug abuse.

Genetic studies have sought to identify subtypes or endophenotypes of schizophrenia in an effort to improve the reliability of findings. A number of chromosomal regions or genes have now been shown to have had replicated linkage to schizophrenia susceptibility. Molecules involved in neurodevelopment or neurotransmitter function are coded by many of the genes that have been implicated in schizophrenia. Studies of neurotransmitter function have identified, among others, a possible role for GABA, glutamate and dopamine in animal models of schizophrenia. GABA neurons that co-express the calcium binding protein parvalbumin have been implicated as have glutamatergic metabotropic receptors and dopamine D3 receptors. Stress influences glutamate and dopamine providing another environmental factor that may interact with the influence of genes on neurotransmitter function. Neurotransmitter interactions include influences on signaling molecules and these too have been implicated in forms of learning thought to be affected in schizophrenia. Results continue to unravel the interplay of genes and environment in the etiology of schizophrenia and other psychotic disorders.

INTRODUCTION: The process of sensorimotor gating is a neurological phenomenon referring to the brain’s ability to process and filter out stimuli in order to prevent an overflow of information. This phenomenon can be operationally measured by prepulse inhibition, which is the attenuation of a stimulus-induced startle response by introducing a milder preceding stimulus. Studies have shown that impairment of prepulse inhibition (PPI) has been correlated with diseases such as schizophrenia and autism spectrum disorder. Many brain areas, including the superior colliculus (SC), inferior colliculus (IC), mediodorsal thalamus (MD), basolateral amygdala (BLA), anterior cingulate cortex (ACC), and ventral hippocampus (VHPC), have been implicated in playing important roles in prepulse inhibition. While many studies have implicated GABA-A receptors in playing a role in PPI regulation, little work has been done on GABA-B receptors. An established rat model with induced prepulse inhibition impairment was used in this study. PPI impairment was induced via injection of the glutamate receptor antagonist dizocilpine. A subgroup of rats was also treated with the antihistamine pyrilamine to reverse the effects of dizocilpine. OBJECTIVES: The aims of this study are to: 1. Expand the understanding of prepulse inhibition in the context of neurological and developmental diseases such as autism spectrum disorder (ASD) and schizophrenia; 2. Identify potential significant differences within GABA-B receptor densities in the rat SC, IC, MD, BLA, ACC, or VHPC between treatment groups with and without dizocilpine and groups with and without pyrilamine. METHODS: Histological brain slides harvested from 36 Sprague-Dawley rats were provided by Dr. Edward Levin from Duke University’s Neurobehavioral Research Lab for this study. The brain slides were incubated in a radioligand solution specific for GABA-B receptors and exposed to autoradiograph film for approximately 12 weeks. The films were developed in a dark room and scanned electronically. GABA-B receptor densities were measured from the images and the data was analyzed using ANOVA and independent T tests. RESULTS: ANOVA testing revealed significant differences between treatment groups in the MD and VHPC. However, only the MD was found to have significant GABA-B receptor differences when comparing the dizocilpine and pyrilamine treatment groups to the control group. The VHPC was found to have significant differences in GABA-B receptor densities when directly comparing the dizocilpine group to the pyrilamine treatment group, rather than to the control group. There were no significant differences in GABA-B receptor densities as a result of either dizocilpine or pyrilamine treatment in the SC, IC, BLA, ACC, or VHPC. CONCLUSION: Changes in GABA-B receptor levels appear to play a role in both the impairment and rescue of PPI in the rat MD. It does not appear to play a role in the SC, IC, BLA, ACC, or VHPC for either the impairment or rescue of PPI function.

Arbetsminne och flertalet exekutiva funktioner är avhängiga varandra; en av dessa funktioner är förmågan till tankesuppression, det vill säga att kunna hålla tillbaka tankar som är irrelevanta för sammanhanget. Detta är en viktig förmåga att ha när vi lär in ny information, eftersom tidigare inlärd information kan blandas ihop med ny, vilket gör det svårt för arbetsminnet att sortera bland de olika stimulusen eller den information som aktuellt hålls där. Detta kallas för proaktiv interferens. Syftet med denna studie var att undersöka potentiella samband mellan proaktiv interferens, ruminering, tankesuppression och neurotransmittorn GABA. För datainsamlingen användes beteendetestet 2-back som mäter proaktiv interferens, självskattningsformulären RRS-BR som mäter ruminering och WBSI som mäter tankesuppression samt MR-kamera som mäter GABA. 31 deltagare, både äldre och yngre, rekryterades till denna studie. Korrelationsanalyser kunde påvisa en signifikant medelstark positiv korrelation mellan GABA och svårighet för tankesuppression, samt en signifikant stark positiv korrelation mellan svårighet för tankesuppression och ruminering. Mediationsanalys visade att tankesuppression medierar förhållandet mellan GABA och ruminering.

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