Current Psychopharmacology - Volume 1, Issue 3, 2012

Fumaria indica is an Ayurvedic medicinal plant widely used for medicinal purposes by practitioners of many traditionally known health care systems. Earlier we reported anxiolytics-like and stress-alleviating activities of a hydro alcoholic extract of this plant (FI; analytically characterized by its contents of fumaric acid and fumarates; ca. 0.8% in total). In the present study, potential anti-aggressive activity of FI was tested in behavior tests, and efforts were made to identify the involved neurochemical mechanisms. Lorazepam like anti-aggressive effects of seven repeated daily doses of FI (100, 200 and 400 mg/kg/day, p.o.) were observed in all the four tests name foot-shock induced aggression, isolationinduced aggression, apomorphine-induced aggression, and aggression in a resident-intruder paradigm. Statistically significant effects were observed even at the lowest dose tested (100 mg/kg). The effects of the highest dose tested (400 mg/kg) were similar to those of the lorazepam dose (2.5 mg/kg; p.o.). Seven oral daily treatments of rats with FI dose dependently increased benzodiazepine receptor density in their pre-frontal cortex. Such treatment also specifically increased serotonin levels in rat prefrontal cortex, whereas dopamine levels were specifically reduced in rat striatum. These observations indicate that the benzodiazepine receptors as well as brain region specific regulatory mechanisms involved in serotonin and dopamine metabolism are involved in the observed anti-aggressive activity of FI.

Since the initial discovery of the first antidepressants in the 1950s, at least two generations of these medications have come to market. Following a brief historical introduction, this paper reviews the first- and second-generation (FGA and SGA) antidepressant medications and their class-related and individual side effect profiles. Class-related adverse reactions include dietary interactions of monoamine oxidase inhibitors (MAOIs) with tyramine, cardiovascular toxicities of the FGAs, and the behavioral syndrome and sexual dysfunction produced by selective serotonergic reuptake inhibitors (SSRIs). Adverse effects common to the different classes include discontinuation syndromes, possible cognitive impairment, suicidality, and a variety of cardiovascular, gastrointestinal and motoric disturbances. Recent reports of side effects elicited by specific agents are noted. Current concerns raised by antidepressant use in pregnancy are discussed. Recent criticisms of the effectiveness claims of antidepressants are summarized. These include the significant placebo contribution to antidepressant outcomes and the ongoing debate about the long-term usefulness of psychotropic medications in general. Most relevant to antidepressants is the recently proposed phenomenon of “tardive dysphoria” that may occur after prolonged antidepressant use and promote resistance to further treatment.

The blood-brain barrier is the structure that maintains central nervous system homeostasis; it is composed of brain endothelial cells, astroglia, pericytes, microglia, and of the extracellular matrix components basal lamina and glycocalyx. The blood-brain barrier constitutes the main interface between the brain and the periphery; therefore it is the main structure regulating the passage of molecules from blood-to-brain and vice versa. At brain endothelial cells are expressed numerous members of the solute carrier (SLC) and ATP-binding cassette (ABC) gene families; those carriers exert selective transport and preclude free exchange of molecules from blood-to-brain. In addition, brain endothelial cells present low paracellular diffusion and vesicle-mediated transport. The regulation of the blood-brain barrier permeability is essential to guarantee nutrient supply to brain cells, but also to allow selective passage of drugs designed to treat brain diseases. This review describes both the pharmacological and physiological approaches to modulate the permeability of the blood-brain barrier. Finally we propose that once more data on blood-brain barrier normal physiology are obtained, health professionals will be able to take advantage of normal variations in blood-brain barrier permeability to administer drugs aimed to affect the central nervous system in the critical time window of blood-brain barrier “opening”.

Cerebrovascular disease is the third leading cause of death and disability in many countries of the first world because currently a safe and effective treatment is still not available for this disease. Cerebrovascular disease is the third leading cause of death in Cuba and the leading cause of disability, as it affects 50% of the population over 60 years. The mortality rate increases exponentially with age, doubling every five years. This tends to prevail in our country, where 14% of the population is over 60 years, with a life expectancy of close to 80. In this paper, we offer a critical opinion on the advantages of employing nasal Neuro-EPO over the more frequently used intravenous Erythropoietin as a neuroprotector for the treatment of acute ischemic stroke. The preclinical results obtained with this new molecule support a rapid delivery to the central nervous system, as well as its efficacy and safety in different animal models. Particular emphasis is made on the possibilities of this new drug in the development of novel treatments for chronic diseases and its potential preventive use in neurodegenerative and psychiatric diseases. It assesses comparatively, the state of the art in relation to the development achieved in our country and the prospects of the use of Neuro-EPO for the treatment and/or prevention of a disease that is virtually orphan of a specific treatment. Finally, recombinant human erythropoietin reaches the central nervous system with great difficulty through transmembrane diffusion or by saturable transport mechanisms, so Neuro- EPO would be an ideal candidate to develop its passage through extracellular pathways, specifically the nasal route

Understanding of the neurobiology of autism spectrum disorders (ASD) is crucial for developing effective treatments. Comparative developmental studies of socio-emotional behaviors provides an endophenotype relevant to understand the core symptoms of ASD. Social interactions are a fundamental aspect of human and animal behavior. We described a multi-behavior parameter integration method and applied it to female-male interaction of adult common marmosets. The behavior category change positively correlated with serum cortisol and progesterone levels after social interaction. A pharmacologic treatment and the evaluation of its efficacy on ASD patient has led to find its neurobiological and pathophysiological foundation. In this review, we summarize the clinical efficacy of risperidone solution, oxytocin, and dietary supplementation with large doses of arachidonic acid added to osahexaenoic acid for impaired social interaction in autism spectrum disorders (ASD). ASD is characterized by impaired social interaction, socialization, and restrictive and repetitive behaviors. Increases over time in the frequency of these disorders (to present rates of about 1 case per 100 children) might be attributable to factors such as new administrative classifications, and increased awareness, early identification. It is important to note that risperidone solution, intranasal administration of oxytocin, and dietary supplementation with large doses of arachidonic acid added to osahexaenoic acid have been reported to improve impaired social interaction. In addition, atypical antipsychotics aripiprazole and SSRI fluoxetine were useful in treating some aspects of social relatedness or the core deficits of communication and socialization. Administration of the anti-androgenic medication leuprolide acetate significantly helped to ameliorate clinical symptoms/behaviors of hyperandrogenemia in some subjects with ASD. The evaluation of treatments for ASD should be directed at neurobiological targets known to be important in the brain's response to abnormal developmental trajectories or toward enhancing plasticity during the highly sensitive period in gene-environment interaction (epigenetic mechanism). Further knowledge of neurobiology and effective treatments for ASD are required.

A test-retest protocol of an animal model of anxiety induces an increase of anxious behaviour and a loss of benzodiazepine induced effect. This effect mainly observed in the elevated plus maze, an ethological model of anxiety in mice, but also in the four plate test, a model based on punishment, was called the one trial tolerance. In the first step, a review of some hypotheses based on behavioural, pharmacological and neurochemical approaches is proposed to explain this benzodiazepines tolerance phenomenon on a test-retest model of anxiety, namely the four-plate test. Aversive memory consists of a diminution of the number of accepted punished passages. “One trial tolerance” is the abolishment of the anxiolytic-like effect of a drug in experimented mice. Diazepam, a usual benzodiazepine affected by one trial tolerance, is used in parallel with DOI, a 5-HT2A agonist that keeps its anxiolytic-like effect during retest, in order to study this phenomenon. Local injection of DOI and diazepam revealed that hippocampus was activated by DOI. Diazepam was active when injected into lateral nuclei of amygdala in naive mice, and into periaqueductal gray matter in experiment mice. These results suggest that aversive memory and one trial tolerance seem triggered via different mechanisms, supported by different structures.

After the experience of a traumatic event, children and adolescents are especially vulnerable to developing debilitating symptoms of Posttraumatic Stress Disorder (PTSD). Criteria for diagnosing this disorder in the pediatric population have proven insufficiently sensitive for children, especially those who are very young. Age-related PTSD symptom expression suggests PTSD assessment and treatment requires developmental consideration. Preschool age children, school age children, adolescents, and adults also possess potentially distinct differences from one another in pharmacokinetics, psychosocial influences, and neurobiology. Pharmacotherapy is often indicated for use in the treatment of pediatric PTSD. Extrapolation of evidence in adult literature for safety, tolerability, and efficacy is nonlinear and should not substitute for dedicated drug trials in pediatric PTSD. This paper reviews all identified randomized controlled trials (RCTs), uncontrolled and open label trials, and case reports/series regarding pharmacotherapy in this population. Emphasis is placed on methodologic rigor and developmental consideration. These trials are discussed in sufficient detail to inform readers of their relative strengths and weaknesses, and of the generalizability of the studies’ conclusions. This review summarizes reports by drug class and developmental cohorts (preschool age, school age, and adolescents). The review will help clinicians a) decide when medications are needed, b) understand current evidence-based alternatives and c) utilize a developmental approach in the selection of medication.