Cannabinoids differentially modulate behavioral and developmental responses to ethanol in Drosophila

Prolonged prenatal or adult exposure to ethanol is detrimental to mental and physical well-being, resulting in developmental abnormalities, progressive addiction and ultimate death. A growing number of studies have shown the therapeutic potential of cannabinoids in ethanol-related behaviors in mammals. However, the potential pharmacological actions of cannabinoids in ethanol responses have not been examined in the model organism Drosophila melanogaster. Here, we systematically investigated the effects of various cannabinoids on ethanol preference, ethanol sensitivity and tolerance, and ethanol-induced developmental defect in Drosophila. We showed that treatment with the phytocannabinoid cannabidiol (CBD) displayed a significant decrease in preference for consuming ethanol in adult flies. Interestingly, cannabinoids exhibited differential roles in short- and long- term ethanol tolerance in flies. Although cannabinoids had no detectable effects on short-term ethanol tolerance, CBD and the endocannabinoid anandamide (AEA) suppressed long-term tolerance to ethanol. Moreover, ethanol exposure delayed larval-to-pupal development and increased larval/pupal size. Unexpectedly, treatment with CBD or endocannabinoids did not attenuate ethanol-induced developmental delay, instead, exacerbated its detrimental effect. Thus, our systematical study reveals, for the first time, a differential role of the cannabinoids in the modulation of ethanol-related responses in Drosophila.

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Integrating Focusing and Differentiation: A Therapeutic Path for Couples in Intimate Relationships

International Journal of Psychotherapy, Counselling and Psychiatry: Theory Research & Clinical Practice ◽

10.35996/1234/3/focusingdifferentiation ◽

2018 ◽

Vol 3 ◽

Author(s):

Evi Zohar

Keyword(s):

Couples Therapy ◽

Therapeutic Potential ◽

Well Being ◽

Point Of View ◽

The Body ◽

Self Awareness ◽

Emotional Healing ◽

Felt Sense ◽

Inner World

Continuing the workshop I've given in the WPC Paris (2017), this article elaborates my discussion of the way I interlace Focusing with Differentiation Based Couples Therapy (Megged, 2017) under the systemic view, in order to facilitate processes of change and healing in working with intimate couples. This article presents the theory and rationale of integrating Differentiation (Bowen, 1978; Schnarch, 2009; Megged, 2017) and Focusing (Gendlin, 1981) approaches, and its therapeutic potential in couple's therapy. It is written from the point of view of a practicing professional in order to illustrate the experiential nature and dynamics of the suggested therapeutic path. Differentiation is a key to mutuality. It offers a solution to the central struggle of any long term intimate relationship: balancing two basic life forces - the drive for individuality and the drive for togetherness (Schnarch, 2009). Focusing is a body-oriented process of self-awareness and emotional healing, in which one learns to pay attention to the body and the ‘Felt Sense’, in order to unfold the implicit, keep it in motion at the precise pace it needs for carrying the next step forward (Gendlin, 1996). Combining Focusing and Differentiation perspectives can cultivate the kind of relationship where a conflict can be constructively and successfully held in the inner world of each partner, while taking into consideration the others' well-being. This creates the possibility for two people to build a mutual emotional field, open to changes, permeable and resilient.

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UNC-18 Modulates Ethanol Sensitivity in Caenorhabditis elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e08-07-0689 ◽

2009 ◽

Vol 20 (1) ◽

pp. 43-55 ◽

Cited By ~ 24

Author(s):

Margaret E. Graham ◽

Mark R. Edwards ◽

Lindy Holden-Dye ◽

Alan Morgan ◽

Robert D. Burgoyne ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Point Mutations ◽

Ethanol Exposure ◽

Snare Complex ◽

Motor Dysfunction ◽

Mouse Strains ◽

Ethanol Sensitivity ◽

Ethanol Preference ◽

Protein Receptor ◽

Acute Ethanol

Acute ethanol exposure affects the nervous system as a stimulant at low concentrations and as a depressant at higher concentrations, eventually resulting in motor dysfunction and uncoordination. A recent genetic study of two mouse strains with varying ethanol preference indicated a correlation with a polymorphism (D216N) in the synaptic protein Munc18-1. Munc18-1 functions in exocytosis via a number of discrete interactions with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein syntaxin-1. We report that the mutation affects binding to syntaxin but not through either a closed conformation mode of interaction or through binding to the syntaxin N terminus. The D216N mutant instead has a specific impairment in binding the assembled SNARE complex. Furthermore, the mutation broadens the duration of single exocytotic events. Expression of the orthologous mutation (D214N) in the Caenorhabditis elegans UNC-18 null background generated transgenic rescues with phenotypically similar locomotion to worms rescued with the wild-type protein. Strikingly, D214N worms were strongly resistant to both stimulatory and sedative effects of acute ethanol. Analysis of an alternative Munc18-1 mutation (I133V) supported the link between reduced SNARE complex binding and ethanol resistance. We conclude that ethanol acts, at least partially, at the level of vesicle fusion and that its acute effects are ameliorated by point mutations in UNC-18.

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Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance

10.1101/205666 ◽

2017 ◽

Author(s):

Pratik Adhikari ◽

Donnoban Orozco ◽

Fred W. Wolf

Keyword(s):

Gene Expression ◽

Behavioral Plasticity ◽

Ethanol Tolerance ◽

Early Response ◽

Ethanol Exposure ◽

Early Gene ◽

Immediate Early ◽

Ethanol Preference ◽

Acute Ethanol ◽

Drug Naïve

Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase terminates Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body α/β neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.

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Sub-acute and long-term effects of ayahuasca on mental health and well-being in healthy ceremony attendants: A replication study

Journal of Psychedelic Studies ◽

10.1556/2054.2021.00174 ◽

2021 ◽

Cited By ~ 1

Author(s):

Kim I. van Oorsouw ◽

Malin V. Uthaug ◽

Natasha L. Mason ◽

Nick J. Broers ◽

Johannes G. Ramaekers

Keyword(s):

Mental Health ◽

Therapeutic Potential ◽

Well Being ◽

Altered States Of Consciousness ◽

Altered States ◽

Long Term Effects ◽

States Of Consciousness ◽

First Time ◽

Health And Well Being

Abstract Background and aims There is a growing body of evidence suggesting that the psychedelic plant tea, ayahuasca, holds therapeutic potential. Uthaug et al. (2018) demonstrated that a single dose of ayahuasca improved mental health sub-acutely and 4-weeks post-ceremony in healthy participants. The present study aimed to replicate and extend these findings. A first objective was to assess the sub-acute and long-term effects of ayahuasca on mental health and well-being in first-time and experienced users. A second aim was to extend the assessment of altered states of consciousness and how they relate to changes in mental health. Method Ayahuasca ceremony attendants (N = 73) were assessed before, the day after, and four weeks following the ceremony. Results We replicated the reduction in self-reported stress 4-weeks post ceremony, but, in contrast, found no reduction in depression. Also, increased satisfaction with life and awareness the day after the ceremony, and its return to baseline 4 weeks later, were replicated. New findings were: reduced ratings of anxiety and somatization, and increased levels of non-judging 4-weeks post-ceremony. We replicated the relation between altered states of consciousness (e.g., experienced ego dissolution during the ceremony) and mental health outcomes sub-acutely. The effects of ayahuasca did not differ between experienced and first-time users. Conclusion Partly in line with previous findings, ayahuasca produces long-term improvements in affect in non-clinical users. Furthermore, sub-acute mental health ratings are related to the intensity of the psychedelic experience. Although findings replicate and highlight the therapeutic potential of ayahuasca, this needs to be confirmed in placebo-controlled studies.

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The genetic relationships between ethanol preference, acute ethanol sensitivity, and ethanol tolerance inDrosophila melanogaster

Fly ◽

10.4161/fly.5.3.16987 ◽

2011 ◽

Vol 5 (3) ◽

pp. 191-199 ◽

Cited By ~ 29

Author(s):

Anita V. Devineni ◽

Kimberly McClure ◽

Douglas Guarnieri ◽

Ammon Corl ◽

Frederick Wolf ◽

...

Keyword(s):

Ethanol Tolerance ◽

Genetic Relationships ◽

Ethanol Sensitivity ◽

Ethanol Preference ◽

Acute Ethanol

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Improving Feeding Outcomes in the NICU: Moving From Volume-Driven to Infant-Driven Feeding

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd19.3.68 ◽

2010 ◽

Vol 19 (3) ◽

pp. 68-74 ◽

Cited By ~ 9

Author(s):

Catherine S. Shaker

Keyword(s):

Intensive Care Unit ◽

Dynamic Systems ◽

Neonatal Intensive Care ◽

Well Being ◽

Dynamic Systems Theory ◽

Feeding Problems ◽

Care Giving ◽

Extremely Preterm ◽

Extremely Preterm Infants

Current research on feeding outcomes after discharge from the neonatal intensive care unit (NICU) suggests a need to critically look at the early underpinnings of persistent feeding problems in extremely preterm infants. Concepts of dynamic systems theory and sensitive care-giving are used to describe the specialized needs of this fragile population related to the emergence of safe and successful feeding and swallowing. Focusing on the infant as a co-regulatory partner and embracing a framework of an infant-driven, versus volume-driven, feeding approach are highlighted as best supporting the preterm infant's developmental strivings and long-term well-being.

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Intraindividual Variability and Stability of Affect and Well-Being

GeroPsych ◽

10.1024/1662-9647/a000094 ◽

2013 ◽

Vol 26 (3) ◽

pp. 185-199 ◽

Cited By ~ 40

Author(s):

Christina Röcke ◽

Annette Brose

Keyword(s):

Age Differences ◽

Well Being ◽

Subjective Well Being ◽

Emotional Experiences ◽

Short Term ◽

Regulatory Processes ◽

Functional Implications ◽

Methodological Approaches ◽

Underlying Processes

Whereas subjective well-being remains relatively stable across adulthood, emotional experiences show remarkable short-term variability, with younger and older adults differing in both amount and correlates. Repeatedly assessed affect data captures both the dynamics and stability as well as stabilization that may indicate emotion-regulatory processes. The article reviews (1) research approaches to intraindividual affect variability, (2) functional implications of affect variability, and (3) age differences in affect variability. Based on this review, we discuss how the broader literature on emotional aging can be better integrated with theories and concepts of intraindividual affect variability by using appropriate methodological approaches. Finally, we show how a better understanding of affect variability and its underlying processes could contribute to the long-term stabilization of well-being in old age.

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