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- Identification of the CART neuropeptide circuitry processing TMT-induced predator stress. [JOURNAL ARTICLE]
- Psychoneuroendocrinology 2014 Sep 2.:194-208.
Abundance of cocaine- and amphetamine-regulated transcript (CART) neuropeptide in the limbic areas like the olfactory system, central nucleus of amygdala (CeA), ventral bed nucleus of stria terminalis (vBNST) and the hypothalamus suggests involvement of the peptide in emotive processing. We examined the role of CART in mediating fear, a strong emotion with profound survival value. Rats, exposed to 2,4,5-trimethyl-3-thiazoline (TMT), a predator related cue extracted from fox feces, showed significant increase in freezing, escape and risk assessment behavior, whereas grooming was reduced. Neuronal activity was up-regulated in the CeA and vBNST in terms of increased immunoreactivity in CART elements and c-Fos expression. Increased expression of both the markers was also seen in some discrete magnocellular as well as parvicellular subdivisions of the paraventricular nucleus (PVN). However, CART containing mitral cells in the main or accessory olfactory bulb did not respond. CART antibody was stereotaxically injected bilaterally into the CeA to locally immunoneutralize endogenous CART. On exposure to TMT, these rats showed reduced freezing, risk assessment and escape behavior while grooming was restored to normal value. We suggest that the CART signaling in the CeA and vBNST, but not in the olfactory system, might be an important component of the innate fear processing, and expression of stereotypic behavior, while CART in the PVN subdivisions might mediate the neuroendocrine response to predator stress.
- Evidence for Fibroblast Growth Factor-2 as a Mediator of Amphetamine-Enhanced Motor Improvement following Stroke. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e108031.
Previously we have shown that addition of amphetamine to physical therapy results in enhanced motor improvement following stroke in rats, which was associated with the formation of new motor pathways from cortical projection neurons of the contralesional cortex. It is unclear what mechanisms are involved, but amphetamine is known to induce the neuronal release of catecholamines as well as upregulate fibroblast growth factor-2 (FGF-2) expression in the brain. Since FGF-2 has been widely documented to stimulate neurite outgrowth, the present studies were undertaken to provide evidence for FGF-2 as a neurobiological mechanism underlying amphetamine-induced neuroplasticity. In the present study rats that received amphetamine plus physical therapy following permanent middle cerebral artery occlusion exhibited significantly greater motor improvement over animals receiving physical therapy alone. Amphetamine plus physical therapy also significantly increased the number of FGF-2 expressing pyramidal neurons of the contralesional cortex at 2 weeks post-stroke and resulted in significant axonal outgrowth from these neurons at 8 weeks post-stroke. Since amphetamine is a known releaser of norepinephrine, in vitro analyses focused on whether noradrenergic stimulation could lead to neurite outgrowth in a manner requiring FGF-2 activity. Primary cortical neurons did not respond to direct stimulation by norepinephrine or amphetamine with increased neurite outgrowth. However, conditioned media from astrocytes exposed to norepinephrine or isoproterenol (a beta adrenergic agonist) significantly increased neurite outgrowth when applied to neuronal cultures. Adrenergic agonists also upregulated FGF-2 expression in astrocytes. Pharmacological analysis indicated that beta receptors and alpha1, but not alpha2, receptors were involved in both effects. Antibody neutralization studies demonstrated that FGF-2 was a critical contributor to neurite outgrowth induced by astrocyte-conditioned media. Taken together the present results suggest that noradrenergic activation, when combined with physical therapy, can improve motor recovery following ischemic damage by stimulating the formation of new neural pathways in an FGF-2-dependent manner.
- Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants. [Journal Article, Review]
- Psychol Res Behav Manag 2014.:223-49.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by symptoms of inattention, hyperactivity, and impulsivity that cause functional impairment. Recent research indicates that symptoms persist into adulthood in the majority of cases, with prevalence estimates of approximately 5% in the school age population and 2.5%-4% in the adult population. Although students with ADHD are at greater risk for academic underachievement and psychosocial problems, increasing numbers of students with ADHD are graduating from high school and pursuing higher education. Stimulant medications are considered the first line of pharmacotherapy for individuals with ADHD, including college students. Although preliminary evidence indicates that prescription stimulants are safe and effective for college students with ADHD when used as prescribed, very few controlled studies have been conducted concerning the efficacy of prescription stimulants with college students. In addition, misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. The purpose of the present systematic review was to investigate the efficacy of prescription stimulants for adolescents and young adults with ADHD and the nonmedical use and misuse of prescription stimulants. Results revealed that both prostimulant and stimulant medications, including lisdexamfetamine dimesylate, methylphenidate, amphetamines, and mixed-amphetamine salts, are effective at reducing ADHD symptoms in adolescents and adults with ADHD. Findings also suggest that individuals with ADHD may have higher rates of stimulant misuse than individuals without the disorder, and characteristics such as sex, race, use of illicit drugs, and academic performance are associated with misuse of stimulant medications. Results also indicate that individuals both with and without ADHD are more likely to misuse short-acting agents than long-acting agents. These findings have implications for intervention, prevention, and future research.
- Common ocular effects reported to a poison control center after systemic absorption of drugs in therapeutic and toxic doses. [JOURNAL ARTICLE]
- Curr Opin Ophthalmol 2014 Sep 15.
Ocular effects resulting from medications assist toxicologists in determining substances involved when treating a poisoned patient. The intention of this review is to discuss the most common ocular effects, the medications that cause them, and the mechanisms by which they occur.According to National Poison Data System, the most common reported ocular effects following a drug ingestion/injection/inhalation are mydriasis, miosis, and nystagmus. The most common drug/drug classes reported to a regional poison control center causing these ocular effects include the following: first, mydriasis - amphetamines and diphenhydramine; second, miosis - clonidine and opioids; third, nystagmus - dextromethorphan. However, many other drugs/substances can cause these effects along with other systemic effects.Ocular findings are a pertinent component of any patient assessment involving therapeutic and/or toxic exposure to medications and other substances.
- P-66characteristics of in-patients with ADHD and substance use disorder: a retrospective study. [Journal Article]
- Alcohol Alcohol 2014 Sep.:i66.
Attention Deficit Hyperactivity Disorder (ADHD) is a major risk factor for the development of substance use disorders (SUD). Patients with both ADHD and SUD become addicted at a younger age, use more substances and are hospitalized more often than SUD patients without ADHD. However, in clinical practice ADHD patients with SUD are not diagnosed sufficiently, especially in adulthood. This study aims to evaluate characteristics of ADHD patients with SUD.This is a retrospective, non-randomized study. All the files of the patients who had applied for treatment for substance use disorders were screened. The patients who had been suffering just for alcoholism were excluded. The patients who had illegal substance use were included and divided into two groups. The first group was consisted with the patients who had both ADHD and SUD together. The second group was consisted with the patients who had only SUD. All the files of the patients were screened for onset of SUD, substance preferences, comorbid psychiatric disorders and history of family SUD .Of the 72 patients were affected by SUD (57 males and 15 females), 55 of them were met the ADHD criteria according to DSM-IV. No statistical significant differences were observed between ADHD and non-ADHD subjects as far as mean age, gender, education level were concerned. The two groups did not show any significant differences in primary substance choice. Cannabis was the most commonly used substance for abuse and dependence. We divided drugs into different categories such as cannabis, heroin, hallucinogen, amphetamine, volatile, nicotine, alcohol, cocaine and no statistical significant differences were found between ADHD and non-ADHD groups (all values, p > 0.05). Using ecstasy showed statistically significant difference between ADHD and non-ADHD groups [χ(2) (1) = 4.124, p<0.05]. ADHD group uses ecstasy significantly higher than the non-ADHD group. There was no statistical difference between ADHD and non-ADHD groups about history of substance abuse and psychiatric disorders in their families (all values, p>0.05). Abuse of synthetic cannabinoids were found significantly different between ADHD group and non-ADHD group [χ(2) (1) = 5.493, p < 0.05]. ADHD group uses synthetic cannabinoids significantly higher than the non-ADHD group. The age of onset of substance use in ADHD and non-ADHD groups differed significantly [χ(2) (1)= 32,998 p < 0.001]. Subjects with ADHD had an earlier onset of SUD compared to the subjects of non- ADHD. Most of the ADHD group starts using illicit drugs before 15 years of age.Findings of this study consistent with previous studies reported that ADHD can be considered as an important risk factor for the development of addiction.The results of the present study show that ADHD is not rare among the patients with SUD who are seeking treatment. Moreover, even if the patient suffers just only for SUD he/she should be evaluated for ADHD for an effective treatment.
- P-42should sustained release preparations start before or after alcohol and opiate addictions? [Journal Article]
- Alcohol Alcohol 2014 Sep.:i61.
The use of long acting naltrexone implants has been shown to reduce the opiate overdoes risk in the first 120 days post implantation (Kelty & Hulse, 2012). However, there is still debate as to when best to prescribe naltrexone implants after detox. The current instruction for use for both oral and depot injections, recommends that the patient be opiate and/or alcohol free for a period of 7-10 days before use. This period between detox and naltrexone use, represents a high risk of opiate overdose death to the patient, as reported in one of our own clinical studies (Kunoe, N. 2009), where a patient scheduled to receive a naltrexone implant, died from a opiate overdose in this time period post detox. Within an outpatient programme based in Perth, Australia (www.freshstart.org.au), more than 1000 detox events are carried out each year for patients stopping opiates, alcohol and amphetamines. In order to prevent deaths that occur between detox and naltrexone insertion all patients are treated prior to a formal detox. Using this method, no deaths have been recorded during detox in a 16 year outpatient program. The protocols to facilitate safe detox and allow sustained naltrexone preparations prior to detox will be discussed.
- P-41protocols for subcutaneous flumazenil use in patients with benzodiazepine and alcohol addiction. [Journal Article]
- Alcohol Alcohol 2014 Sep.:i61.
In Perth Australia, we provide a large addiction service committed to assisting patients stop their polydrug addictions. With a treatment service that regularly treats a combination of alcohol, amphetamines, opiates, cannabis and benzodiazepines addictions, rarely do these addictions occur by themselves. The protocols that we have developed at our outpatient clinic in Perth have evolved using the principal of ceasing first the opiate, alcohol and/or the amphetamine addiction with the use of long acting naltrexone implants. Secondly, the patient's benzodiazepine dependency is targeted with the use of subcutaneous flumazenil. The treatment protocols developed within this service and the treatment outcomes achieved will be presented.
- Sy03-1-4isam fellowship 5 years of legal highs in romania - consequences and solutions. [Journal Article]
- Alcohol Alcohol 2014 Sep.:i5.
Since 2009 "legal highs", mainly amphetamine type stimulants (ATS) have produced major changes in the epidemiology and morbidity of intravenous drugs in Romania. Unfortunately the authorities were not able to finance adequate measures for the challenge.We have gathered all the evidence from different sources, official data, NGO's working in the field, published materials and also grey literature, in order to put up a real frame of the problem and try to convince in the last moment the authorities to finance the most efficient interventions.In the last 5 years we had a stable population of problematic drug users (PDU) of 20,000, but we have seen a shift from 96% opiate users to 49% ATS users. Due to an increase in the number of daily injecting to ∼6/day and a cut in needle exchange programs (NEP) we have seen a 10 time increase in the number of HIV new cases and a doubling of the mortality among IDU's.After 3 joint EMCDDA, ECDC and local specialists meetings the necessity of a major increase in the NEP funding in order to reach 200 syringes/year/estimated POU and at least a doubling the numbers of OST places are urgently needed.
- Or10-5drug use characteristics of opioid and amphetamine-type stimulants (coats) dependent individuals in kota bahru, malaysia. [Journal Article]
- Alcohol Alcohol 2014 Sep.:i48.
More than 60% of opioid IDUs in many regions in Malaysia use amphetamine type stimulants (ATS) and 29% of opioid IDUs inject ATS. In Kota Bharu, approximately 65% of patients entering buprenorphine or methadone maintenance treatment have current ATS abuse or dependence at treatment. The objective of this study is to describe the drug use characteristics of COATS individuals.A survey was conducted among n = 88 COATS dependent individuals who were interested to enter and undergo treatment in Hospital Universiti Sains Malaysia in Kota Bharu.Their mean (SD) age was 35.3 (8) years, 80% had between 7 to 9 years of education, 14.1% reported to be HIV positive while 30% have never been tested. 35.2% reported heroin use of less than 10 years; 25.7%, 11 to 15 years; 12.2%, 16 to 20 years and 15.1%, 21 to 25 years. While for ATS use, 48% reported using less than 10 years; 33.3%, 11 to 15 years; 12%, 16 to 20 years. 74% and 35% of them injected heroin and ATS. 35.5% reported to use ATS daily.Individuals in this sample have a relatively long history of drug use and they also report high rates of injection drug use.
- Sy42-5current updates in pharmacotherapy in managing amphetamine-type stimulant (ats) used. [Journal Article]
- Alcohol Alcohol 2014 Sep.:i36.
The latest trend of addiction in Malaysia has been toward used of Amphetamine type stimulant. Various attempt have been used to manage those who were on these drug but it yet to show any good outcome. Psychosocial rehabilitation were the preferred choice by the National Anti-Drug Agencies (NADA) and in many cases it was done through therapeutic community program. Unfortunately it is costly and the relapse rate even after 2 years rehabilitation were almost 95%. The demand for medical therapeutic intervention came after the success of harm reduction program for managing heroin dependence syndrome. In the case of Methamphetamine and other type of ATS Aripiprazole were chosen as the drug of choice in this study. It is an antipsychotic and partial dopamine agonist. Result of this study showed that it is effective to reduce craving among those who were dependence on methamphetamine.