Endocannabinoid Involvement in Impulsivity and Decision-making

Problem gambling is a widespread phenomenon with a prevalence estimate of 2.3% globally (Williams, Volberg, & Stevens, 2012). Although little is known about the neurochemistry underlying this pathological behaviour, evidence suggests that dysregulation of the brain’s endocannabinoid (eCB) system may be implicated in impulsivity and decision-making. For example, chronic cannabis users exhibit impulsive behaviour and impaired decision-making on the Iowa Gambling Task (IGT). The present study sought to further examine the role of the eCB system in problem gambling-related decision-making in laboratory rats using the five-choice serial reaction time task (5-CSRTT), and a recently-developed rodent analogue of the IGT called the rat gambling task (rGT). It was predicted that increasing neural levels of the eCB anandamide by administering the fatty acid amide hydrolase (FAAH) inhibitor URB597 would increase impulsivity as found previously with psychomotor stimulants. Results revealed that URB597 (0.03-1 mg/kg, IP) had no effect on premature responding or correct choices. Cocaine (15 mg/kg, IP) increased premature responding and decreased choice accuracy in the 5-CSRTT, but these effects were not attenuated by the CB1 inverse agonist rimonabant (3 mg/kg, IP). Furthermore, neither URB597 (0.03-1 mg/kg, IP) nor the cannabinoid receptor agonist THC (1.0-1.5 mg/kg, IP) altered optimal choice preference or premature responding in the rGT. Taken together, results did not support the notion that eCBs are involved in impulsivity or decision-making. We also conclude that any involvement of the eCB system in impulsivity is likely a downstream process from dopamine release

Psychotropic Effects of Cannabis Components on the Mesolimbic Dopaminergic System

The two most abundant phytochemical compounds in cannabis are cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC). THC is the primary psychoactive component of cannabis and is a partial CB1 receptor (CB1R) agonist. THC is believed to be responsible for the motivational and dependence-producing effects of cannabis and causes psychotomimetic and affective processing disturbances. Conversely, CBD, is non-psychoactive, acts as a 5-HT1A receptor agonist, antagonizes CB1Rs, and possesses both anti-psychotic and anxiolytic properties. The neural substrate believed to be responsible for many of the effects of cannabis is the dopaminergic, mesolimbic reward pathway which is responsible for the regulation of cognition and emotion. Specifically, the shell region of the nucleus accumbens (NASh) and the ventral tegmental area (VTA) are important brain areas involved in motivation, reward, aversion, and fear-related behavioural processing. Using a combination of behavioural, electrophysiology and molecular techniques, the first chapter evaluates the effects of direct infusions of CBD into the NASh. Intra-NASh CBD blocked the formation of fear memory through a 5-HT1A-dependent mechanism by functionally modulating the activity of neuronal activity dynamics directly in the VTA. In the second chapter, we examined the effects of THC in either the anterior NASh (aNASh), known as the “hedonic hotspot”, or posterior NASh, known to be involved in aversion. We demonstrate that aNASh THC produced rewarding behavioural effects and modulated reward salience through a µ-opioid-receptor-dependent mechanism, whereas THC in the pNASh produced aversive behavioural effects through a k-opioid-receptor-dependent mechanism. ICV infusions of THC caused aNASh MSN activity to decrease and increased the power of ɣ-oscillations on the local field potential but caused pNASh increased MSN activity and decreased the power of ɣ-oscillations on the local field potential. Finally, in the third chapter, we provide a characterization of how THC differentially regulates fear-related memory formation and cognitive processing via distinct Akt-dependent vs. GSK3-dependent signaling pathways, in the aNASh vs. pNASh, respectively. Together, these data provide a novel neuronal, molecular, behavioural and anatomical characterization of the effects of CBD and THC directly within the mesolimbic circuitry and reveals critical new insights into the mechanisms by which THC and CBD regulate affective and cognitive behaviours

Two Poems on Colour

Christopher Norris is Emeritus Professor of Philosophy at Cardiff University. He worked on literary criticism, on the question of realism and antirealism in philosophy, on Derrida and deconstructionism and on the philosophy of science. In the past few years he has also authored several philosophical poems. In this issue we present two poems he wrote that are dedicated to color

Con motivo del Doctorado Honoris Causa de Terry Eagleton, Universidad de Santiago de Compostela, España

My essay–very much in the original, tentative and exploratory sense of the word–takes retrospective stock of Terry Eagleton’s (roughly speaking) early to middle-period work across its dauntingly diverse range of topics. I focus, naturally enough, on those books that have most strongly influenced my own thinking or–as so often–pointed me in new and deeply mind-changing directions. The approach is in part anecdotal as befits a recurrent crossing of paths that has kept me reading his work with a constant sense that, whatever the shifts in my own interest, his latest book or article is likely to open up some fresh and germane line of enquiry. Nobody has done more than Terry over the past fifty years to extend the possibilities of creative inter-disciplinary exchange that opened in the late 1960s and are now being closed down with ferocious zeal by a UK in government in quest of unthinking ideological compliance. In this tribute I focus chiefly on his successive approaches to the question of ideology as it figures not only in literary and cultural theory but in daily praxis and various contexts of communal experience.Mi ensayo –en el sentido original, tentativo y exploratorio de la palabra– hace un balance retrospectivo de la obra de Terry Eagleton (en términos generales) de principios a mediados de su período, en su abrumadora variedad de temas. Me centro, naturalmente en los libros que más han influido en mi propio pensamiento o –como tantas veces– que me han llevado a direcciones nuevas y profundamente cambiantes. El enfoque es en parte anecdótico, como corresponde a un cruce recurrente de caminos que me ha mantenido leyendo su obra con la constante sensación de que, sean cuales sean los cambios en mi propio interés, su último libro o artículo probable- mente abrirá alguna línea de investigación nueva y pertinente. Nadie ha hecho más que Terry en los últimos cincuenta años para ampliar las posibilidades de intercambio creativo interdisciplinario que se abrieron a finales de la década de 1960 y que ahora están siendo cerradas con feroz celo por un Reino Unido en el gobierno en busca de la conformidad ideológica irreflexiva. En este homenaje me centraré principalmente en sus sucesivas aproximaciones a la cuestión de la ideología, tal y como figura no sólo en la teoría literaria y cultural, sino en la praxis cotidiana y en diversos contextos de la experiencia comunitaria

The Ontology of Art: Six submissions

This is a verse-essay in the form of six extended villanelles that discuss various aspects of the relationship between poetry, music, and the visual arts. More specifically they concern issues of ontology, autonomy, endurance, expressive power, and formal resistance to the vicissitudes of cultural change. The rhyme-scheme (tight but highly musical) is used to point up and differentiate the range of aesthetic attributes involved in this running debate.This is a verse-essay in the form of six extended villanelles that discuss various aspects of the relationship between poetry, music, and the visual arts. More specifically they concern issues of ontology, autonomy, endurance, expressive power, and formal resistance to the vicissitudes of cultural change. The rhyme-scheme (tight but highly musical) is used to point up and differentiate the range of aesthetic attributes involved in this running debate

Adversus Mathematicos

A poem about relationship between mathematics and the human experience of time

Ca\u3csup\u3e2+\u3c/sup\u3e, Astrocyte Activation and Calcineurin/NFAT Signaling in Age-Related Neurodegenerative Diseases

Mounting evidence supports a fundamental role for Ca2+ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca2+/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca2+ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and vascular pathology. Similar upregulation of the CN-dependent transcription factor nuclear factor of activated T cells (NFAT4) also appears in activated astrocytes in mouse models of Alzheimer’s disease (ADs) and traumatic brain injury (TBI). Major consequences of hyperactivated CN/NFAT4 signaling in astrocytes are neuroinflammation, synapse dysfunction and glutamate dysregulation/excitotoxicity, which will be covered in this review article

Calcineurin and glial signaling: Neuroinflammation and beyond

Similar to peripheral immune/inflammatory cells, neuroglial cells appear to rely on calcineurin (CN) signaling pathways to regulate cytokine production and cellular activation. Several studies suggest that harmful immune/inflammatory responses may be the most impactful consequence of aberrant CN activity in glial cells. However, newly identified roles for CN in glutamate uptake, gap junction regulation, Ca2+ dyshomeostasis, and amyloid production suggest that CN\u27s influence in glia may extend well beyond neuroinflammation. The following review will discuss the various actions of CN in glial cells, with particular emphasis on astrocytes, and consider the implications for neurologic dysfunction arising with aging, injury, and/or neurodegenerative disease