Arlene S. Eison

Bio: Arlene S. Eison is an academic researcher from Bristol-Myers Squibb. The author has contributed to research in topics: Anxiolytic & Gepirone. The author has an hindex of 16, co-authored 23 publications receiving 1290 citations.

Serotonergic mechanisms in the behavioral effects of buspirone and gepirone.

Abstract: The literature describing the role of serotonin (5-HT) in the mediation of anxiety is a controversial one. Serotonergic involvement in the mechanism of action of two nonbenzodiazepine anxiolytics, buspirone and gepirone, supports a role for serotonin in anxiety. The anticonflict effect of both drugs is blocked by serotonin lesions, and gepirone induces the serotonin syndrome. A shift in the gepirone dose-response curve to the left in serotonin lesioned rats suggests that this may be 5-HT-receptor mediated. Both buspirone and gepirone enhance the acoustic startle response and gepirone's effect is attenuated in serotonin lesioned animals. While other components of buspirone's mechanism of action may suppress the behavioral expression of its serotonergic interactions, results from these studies suggest that serotonin agonist-like activity may be an important mechanism in the actions of a clinically proven nonbenzodiazepine anxiolytic (buspirone), and anxiolytic candidate (gepirone).

Nefazodone: preclinical pharmacology of a new antidepressant.

Abstract: Recent pharmacologic studies suggest that nefazodone may possess antidepressant activity. Nefazodone is active in behavioral models predictive of antidepressant potential. It is active in reversing learned helplessness, prevents reserpine-induced ptosis, and enhances response efficiency in the differential reinforcement for low rates of response paradigm. In in vitro studies, nefazodone inhibits the binding of [3H]ketanserin to cortical serotonin2 (5-HT2) binding sites, whereas in vivo, it antagonizes the 5-HT2-mediated quipazine-induced head shake in rats. In ex vivo studies, acute oral administration of nefazodone inhibits cortical serotonin uptake and occupies frontal cortical 5-HT2 receptor binding sites. Chronic administration of nefazodone produces a reduction in 5-HT2-mediated behavior and decreases cortical 5-HT2 receptor binding site density. Further, a chronic high-dose nefazodone regimen significantly potentiates 5-HT1A-mediated behavioral responses in rats. Nefazodone exhibits decreased anticholinergic, alpha-adrenolytic, and sedative activity relative to other antidepressants.

Serotonergic mechanisms in anxiety

Abstract: Eison, Arlene, S. and Michael S. Eison: Serotonergic Mechanisms in Anxiety. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1994, 18(1): 47–62. 1. 1. Anatomical, behavioral, neurochemical and electrophysiological evidence collectively support a role for central 5-HT in the modulation of anxiety and the anti-anxiety action of the benzodiazepines. 2. 2. The advent of selective agonists and antagonists for 5-HT receptor subtypes (5-HT 1 , 5-HT 2 , 5-HT 3 ) has rekindled investigation of the role of 5-HT in anxiety mechanisms. 3. 3. The azapirones represent a new class of agent which possesses affinity for 5-HT 1A receptors (partial agonists) and is active in anxiolytic animal models as well as in the clinic (buspirone) 4. 4. While preclinical data supporting the anxiolytic potential of 5-HT 2 antagonists remains controversial, a recent clinical study supports ritanserin's anxiolytic effects. 5. 5. Several animal models support the anxiolytic potential of the 5-HT 3 antagonist odansetron (GR38032F). Confirmation of it's therapeutic utility awaits clinical results.

Molecular, pharmacological and functional diversity of 5-HT receptors

Abstract: Serotonin (5-hydroxytryptamine, 5-HT) is probably unique among the monoamines in that its effects are subserved by as many as 13 distinct heptahelical, G-protein-coupled receptors (GPCRs) and one (presumably a family of) ligand-gated ion channel(s). These receptors are divided into seven distinct classes (5-HT(1) to 5-HT(7)) largely on the basis of their structural and operational characteristics. Whilst this degree of physical diversity clearly underscores the physiological importance of serotonin, evidence for an even greater degree of operational diversity continues to emerge. The challenge for modern 5-HT research has therefore been to define more precisely the properties of the systems that make this incredible diversity possible. Much progress in this regard has been made during the last decade with the realisation that serotonin is possibly the least conservative monoamine transmitter and the cloning of its many receptors. Coupled with the actions of an extremely avid and efficient reuptake system, this array of receptor subtypes provides almost limitless signalling capabilities to the extent that one might even question the need for other transmitter systems. However, the complexity of the system appears endless, since posttranslational modifications, such as alternate splicing and RNA editing, increase the number of proteins, oligomerisation and heteromerisation increase the number of complexes, and multiple G-protein suggest receptor trafficking, allowing phenotypic switching and crosstalk within and possibly between receptor families. Whether all these possibilities are used in vivo under physiological or pathological conditions remains to be firmly established, but in essence, such variety will keep the 5-HT community busy for quite some time. Those who may have predicted that molecular biology would largely simplify the life of pharmacologists have missed the point for 5-HT research in particular and, most probably, for many other transmitters. This chapter is an attempt to summarise very briefly 5-HT receptor diversity. The reward for unravelling this complex array of serotonin receptor--effector systems may be substantial, the ultimate prize being the development of important new drugs in a range of disease areas.

Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation

Abstract: Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.

Reduced anxiety‐like behavior and central neurochemical change in germ‐free mice

Abstract: Background There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity. Methods We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity. Key Results Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. Altered GF behavior was accompanied by a decrease in the N-methyl-D-aspartate receptor subunit NR2B mRNA expression in the central amygdala, increased brain-derived neurotrophic factor expression and decreased serotonin receptor 1A (5HT1A) expression in the dentate granule layer of the hippocampus. Conclusions & Inferences We conclude that the presence or absence of conventional intestinal microbiota influences the development of behavior, and is accompanied by neurochemical changes in the brain.