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- Individual differences in the conditioned and unconditioned rat 50-kHz ultrasonic vocalizations elicited by repeated amphetamine exposure. [JOURNAL ARTICLE]
- Psychopharmacology (Berl) 2013 May 23.
RATIONALE:Adult rats often produce 50-kHz ultrasonic vocalizations (USVs), particularly the frequency-modulated varieties, in appetitive situations. These calls are thought by some to reflect positive affective states and the reinforcing value of drugs such as amphetamine and cocaine.
OBJECTIVE:The objective of this study was to determine whether the number of unconditioned 50-kHz USVs elicited by amphetamine predicts the development and/or magnitude of drug-conditioned motivation.
METHODS:In three experiments, we recorded USVs before and after injections of 1 mg/kg amphetamine (i.v. or i.p.) administered once per session. Rats were categorized as "high callers" or "low callers" according to individual differences in the number of 50-kHz USVs elicited by their first amphetamine injection. We examined the conditioned appetitive behavior and conditioned place preference (CPP) that emerged in high and low callers after repeated pairings of amphetamine with specific contexts. We also examined whether amphetamine-induced calling was affected by treatment within an unfamiliar (test chamber) versus familiar (home cage) context.
RESULTS:Within an unfamiliar environment, the high callers consistently produced more amphetamine-induced 50-kHz USVs than the low callers. Compared to the low callers, high callers showed significantly greater amphetamine CPP as well as enhanced conditioned 50-kHz USVs and locomotor activity during anticipation of amphetamine. Individual differences were stable when amphetamine was administered in test chambers, but when it was administered in home cages, low callers showed an increase in 50-kHz calling that matched the high callers.
CONCLUSIONS:These findings suggest that individual differences in drug-induced USVs can reveal environment-sensitive traits involved in drug-related appetitive motivation.
- Characteristics and trends of drug and dietary supplement inquiries by college athletes. [JOURNAL ARTICLE]
- J Am Pharm Assoc (2003) 2013 May 1; 53(3):297-303.
OBJECTIVETo characterize the types of drug and dietary supplement inquiries submitted to the National Center for Drug Free Sport through the Resource Exchange Center (REC). DESIGN Cross-sectional study. SETTING United States, from July 2009 through June 2010. PARTICIPANTS Athletes and athletic personnel associated with the National Collegiate Athletic Association (NCAA). INTERVENTION Tabulation and classification of drugs and dietary supplement inquiries. MAIN OUTCOME MEASURE Characteristics and trends of drug and dietary supplement inquiries.
RESULTSInquiries for prescription medications for albuterol inhalers, methylphenidate, amphetamines, and prednisone were the most common using a drug lookup function. The most common inquiries for over-the-counter medications included pseudoephedrine, loratadine, cetirizine, and caffeine. Among dietary supplements, inquiries for amino acids/metabolites, vitamins and minerals, and herbal products occurred most frequently. One dietary supplement, N.O.-Xplode (Bio-Engineered Supplements and Nutrition, Inc.), accounted for the majority of individual dietary supplement inquiries. Banned substances accounted for 30% of all inquiries submitted to the REC and 18% of medications searched in a drug lookup database.
CONCLUSIONAlmost 25,000 inquiries were submitted to the REC. Pharmacists can use this information to advise, counsel, and refer NCAA athletes regarding the use of banned and permitted substances. Education programs regarding stimulants, dietary supplements, and the risk of using substances such as animal byproducts are needed, and pharmacists can participate in these programs.
- Amphetamine Mechanisms and Actions at the Dopamine Terminal Revisited. [JOURNAL ARTICLE]
- J Neurosci 2013 May 22; 33(21):8923-8925.
- "K2," "Spice," and "Bath Salts" - The In-Vogue Recreational Drugs - What the Intensivists Need to Know. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):340A.
SESSION TYPE: Critical Care Student/Resident Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION:Plants are utilized to derive substances for medical therapy and also recreational use. With advances in science and refinement technologies, more potent compounds that are difficult to detect by traditional assays, have been synthesized. Over 40 new compounds were identified by European authorities in 2010. Of the many available on the internet, K2/SPICE in the Herbal marijuana alternatives (HMA)category and BATH SALTS(BS) or synthetic cathinones , are being increasingly seen in the ER. This indicates not only widespread use with easy availability but their propensity to cause life threatening reactions. As intensivists, we need to be aware of their potential, detection and treatment, both during acute intoxication and withdrawal .
CASE PRESENTATION:37 yr old male with no past medical history was admitted to the ICU with NSTEMI. Within hours he became agitated, aggressive and violent. He had to be sedated with propofol, which in turn required intubation. He required continuous propofol infusion with added benzodiazepines(BZDs) and fentanly dosing for 1 week. He was later found to have used BS. 31 yr old male was admitted with drug overdose and found to have used BS. He required sedation with BZDs along with fentanyl and dexmetomidine and remained intubated for 10 days. 20 yr old male, was admitted for community acquired pneumonia and was subsequently intubated for respiratory failure secondary to ARDS. Family reported synthetic marijuana use. Following extubation he was constantly restless and tachycardic, requiring BZD. It is likely that he was experiencing withdrawal.
DISCUSSION:HMAs are adulterated with synthetic cannabinoids and act by sympathomimetic actions. Brand names are K2 and SPICE. Effects include agitation, paranoia, delusions, tachycardia, diaphoresis. ST-elevation myocardial infarction in adolescents with use of K2 has been reported. Synthetic cannabinoids have serotonin-like and weak monoamine oxidase inhibitor properties, with the potential to cause serotonin syndrome. Withdrawal symptoms include: restlessness, nausea, tremors, sweating and nightmares. Detection is by gas chromatography- mass spectrometry. Treatment is supportive with BZD for severe agitation. BS are known for their amphetamine like effects. Use can be nasally, orally, rectally or intravenously. Effects include heightened alertness, increased energy, sexual arousal and extreme aggression and psychotic behavior. Sympathomimetic effects lead to tachycardia, hypertension, and hyperthermia. MIs and myocarditis have been reported. Drug effect can last for days on repeated re-dosing. Long term effects involve Parkinsonism. Detection is not possible on the traditional drug screens. Treatment involves aggressive supportive measures including heavy sedation against seizures, hyperthermia and other complications.
CONCLUSIONS:Above1) Here Today, Gone Tomorrow and Back Again?. Rosenbaum, C. Etal. Journal of Medical Toxicology. Jan 2012.DISCLOSURE: The following authors have nothing to disclose: Divyashree Varma, Pratik DalalNo Product/Research Disclosure InformationSUNY-Upstate Medical University, Syracuse, NY.
- Bath Salts Intoxication: A Case Series. [JOURNAL ARTICLE]
- Chest 2012 Oct 1; 142(4_MeetingAbstracts):323A.
SESSION TYPE: Critical Care Student/Resident Case Report Posters IPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM
INTRODUCTION:Bath salts are derivatives of cathinone and their toxic effects are largely the same effects seen with amphetamines in large doses. Bath salts can be ingested, smoked or used intravenously. Their use is on the rise and responsible for a large number of emergency room visits. The presentation is similar to other stimulant overdoses, though there may be a more intense degree of delirium associated with bath salt intoxication.
CASE PRESENTATION:Our case series involves five patients (six hospital courses) who presented with bath salts ingestion. The presentations involved signs and symptoms of intense sympathetic response and the hospital course had varied outcomes including cardiac arrest in one case. All patients had a history of drug abuse, and most had psychiatric disorders as well. All patients suffered some degree of delirium, rhabdomyolsis and acute renal failure. Treatments included benzodiazepenes, mechanical ventilation, and intravenous hydration. Three of the five patients had an encounter with law enforcement prior to their arrival at the hospital.
DISCUSSION:Bath salts are available for around twenty dollar packets at truck stops and on the Internet, usually marketed with the disclaimer, "not for human consumption". Symptoms include hallucinogenic-delusional symptoms, extreme agitation, and combativeness. Management is largely supportive and includes aggressive IV hydration, dampening of the excessive sympathetic outflow with benzodiazepines and close monitoring in ICU setting. On Sept. 7, 2011, the U.S. Drug Enforcement Administration (DEA) invoked its "emergency scheduling authority" to control these synthetic stimulants. The DEA plans to make possessing and selling these chemicals, or products that contain them, illegal in the United States.
CONCLUSIONS:Bath salts are one of the growing list of drugs of abuse. Patients can still obtain these legally in many states and despite warnings to not ingest or smoke, this has become a significant problem. The presentation mimics other sympathetic drugs and cause a significant amount of delirium, rhabdomyolysis and visits to the emergency room often leading to hospitalizations.1) Ross EA. "Bath Salts "Intoxication. N Engl J Med. 2011; 365:967-968.2) "Chemicals Used in "Bath Salts" Now Under Federal Control and Regulation." United States Drug Enforcement Administration. 21 Oct 2011.3) Benzie F. "Emergency department visits after use of a drug sold as "bath salts"-Michigan, November, 13, 2010-March 31, 2011. Morb Mortal Wkly Rep. 2011; 60(19):624-627.DISCLOSURE: The following authors have nothing to disclose: Syed Imam, Hetalben Patel, Monay Mahmoud, Nisha Prakash, Matthew King, Richard FremontNo Product/Research Disclosure InformationMeharry Medical College, Nashville, TN.
- Hypothalamic expression of mutant huntingtin contributes to the development of depressive-like behavior in the BAC transgenic mouse model of Huntington's disease. [JOURNAL ARTICLE]
- Hum Mol Genet 2013 May 22.
Psychiatric symptoms such as depression and anxiety are important clinical features of Huntington's disease (HD). However, the underlying neurobiological substrate for the psychiatric features is not fully understood. In order to explore the biological origin of depression and anxiety in HD, we used a mouse model that expresses the human full-length mutant huntingtin, the BACHD mouse. We found that the BACHD mice displayed depressive- and anxiety-like features as early as at 2 months of age as assessed using the Porsolt forced swim test (FST), the sucrose preference test and the elevated plus maze (EPM). BACHD mice subjected to chronic treatment with the anti-depressant sertraline were not different to vehicle-treated BACHD mice in the FST and EPM. The behavioral manifestations occurred in the absence of reduced hippocampal cell proliferation/neurogenesis or upregulation of the hypothalamic-pituitary-adrenal axis. However, alterations in anxiety- and depression-regulating genes were present in the hypothalamus of BACHD mice including reduced mRNA expression of neuropeptide Y, tachykinin receptor 3 and vesicular monoamine transporter type 2 as well as increased expression of cocaine and amphetamine regulated transcript. Interestingly, the orexin neuronal population in the hypothalamus was increased and showed cellular atrophy in old BACHD mice. Furthermore, inactivation of mutant huntingtin in a subset of the hypothalamic neurons prevented the development of the depressive features. Taken together, our data demonstrate that the BACHD mouse recapitulates clinical HD with early psychiatric aspects and point to the role of hypothalamic dysfunction in the development of depression and anxiety in the disease.
- BDNF Over-Expression in the Ventral Tegmental Area Prolongs Social Defeat Stress-induced Cross-Sensitization to Amphetamine and Increases ΔFosB Expression in Mesocorticolimbic Regions of Rats. [JOURNAL ARTICLE]
- Neuropsychopharmacology 2013 May 21.
Social defeat stress induces persistent cross-sensitization to psychostimulants, but the molecular mechanisms underlying the development of cross-sensitization remain unclear. One candidate is brain-derived neurotrophic factor (BDNF). The present research examined whether ventral tegmental area (VTA) BDNF over-expression would prolong the time-course of cross-sensitization after a single social defeat stress, which normally produces transient cross-sensitization lasting less than one week. ΔFosB, a classic molecular marker of addiction, was also measured in mesocorticolimbic terminal regions. Separate groups of intact male Sprague-Dawley rats underwent a single episode of social defeat stress or control handling, followed by amphetamine challenge 3 or 14 days later. AMPH cross-sensitization was apparent 3 but not 14 days after stress. Intra-VTA infusion of adeno-associated viral (AAV-BDNF) vector resulted in a two-fold increase of BDNF level in comparison with the group receiving the control virus (AAV-GFP), which lasted at least 45 days. Additionally, over-expression of BDNF in the VTA alone increased ΔFosB in the nucleus accumbens (NAc) and prefrontal cortex. Fourteen days after viral infusions, a separate group of rats underwent a single social defeat stress or control handling and were challenged with amphetamine (AMPH) 14 and 24 days after stress. AAV-BDNF rats exposed to stress showed prolonged cross-sensitization and facilitated sensitization to the second drug challenge. Immunohistochemistry showed that the combination of virally enhanced VTA BDNF, stress, and AMPH resulted in increased ΔFosB in the NAc shell compared to other groups. Thus, elevation of VTA BDNF prolongs cross-sensitization, facilitates sensitization, and increases ΔFosB in mesocorticolimbic terminal regions. As such, elevated VTA BDNF may be a risk factor for drug sensitivity.Neuropsychopharmacology accepted article preview online, 21 May 2013; doi:10.1038/npp.2013.130.
- A Norwegian Study of the Suitability of Hair Samples in Epidemiological Research of Alcohol, Nicotine and Drug Use. [JOURNAL ARTICLE]
- J Anal Toxicol 2013 May 19.
A feasibility study was performed to examine the effectiveness of hair testing in determining the prevalence of drug use in a young adult population. The study included 200 randomly selected young adults in Norway. It was designed to make the collection, preparation and analysis of the samples as little resource demaning as possible. Full anonymity was provided for the participants. In total, 23.5% of the samples were positive for one or more substances (14.5%, excluding the nicotine metabolite cotinine). Of the samples, 5% were positive for at least one illegal drug, 9.5% for a medicinal drug, 11.5% for cotinine and 2.5% for the alcohol metabolite ethyl glucuronide. The preliminary findings suggest that the study protocol used to collect and analyze the samples was unable to produce results that could be generalized to the young adult population in Norway. Analysis of hair samples may underestimate the use of cannabis, alcohol, amphetamine and methamphetamine. It may, however, be done to estimate cocaine and general drug use if a sample-collection procedure different from that described in our study is used and includes information about hair length, sample length, length from the scalp, cosmetic treatment, washing and whether the samples always get washed/decontaminated prior to analysis.
- A role for α4(non-α6)* nicotinic acetylcholine receptors in motor behavior. [JOURNAL ARTICLE]
- Neuropharmacology 2013 May 17.
Nicotinic acetylcholine receptors (nAChRs) containing either the α4 and/or α6 subunit are robustly expressed in dopaminergic nerve terminals in dorsal striatum where they are hypothesized to modulate dopamine (DA) release via acetylcholine (ACh) stimulation from cholinergic interneurons. However, pharmacological blockade of nAChRs or genetic deletion of individual nAChR subunits, including α4 and α6, in mice, yields little effect on motor behavior. Based on the putative role of nAChRs containing the α4 subunit in modulation of DA in dorsal striatum, we hypothesized that mice expressing a single point mutation in the α4 nAChR subunit, Leu9'Ala, that renders nAChRs hypersensitive to agonist, would exhibit exaggerated differences in motor behavior compared to WT mice. To gain insight into these differences, we challenged WT and Leu9'Ala mice with the α4β2 nAChR antagonist dihydro-β-erythroidine (DHβE). Interestingly, in Leu9'Ala mice, DHβE elicited a robust, reversible motor impairment characterized by hypolocomotion, akinesia, catalepsy, clasping, and tremor; whereas the antagonist had little effect in WT mice at all doses tested. Pre-injection of nicotine (0.1 mg/kg) blocked DHβE-induced motor impairment in Leu9'Ala mice confirming that the phenotype was mediated by antagonism of nAChRs. In addition, SKF 82958 (1 mg/kg) and amphetamine (5 mg/kg) prevented the motor phenotype. DHβE significantly activated more neurons within striatum and substantia nigra pars reticulata in Leu9'Ala mice compared to WT animals, suggesting activation of the indirect motor pathway as the circuit underlying motor dysfunction. ACh evoked DA release from Leu9'Ala striatal synaptosomes revealed agonist hypersensitivity only at α4(non-α6)* nAChRs. Similarly, α6 nAChR subunit deletion in an α4 hypersensitive nAChR (Leu9'Ala/α6KO) background had little effect on the DHβE-induced phenotype, suggesting an α4(non-α6)* nAChR-dependent mechanism. Together, these data indicate that α4(non-α6)* nAChR have an impact on motor output and may be potential molecular targets for treatment of disorders associated with motor impairment.
- A national study of substance use behaviors among NCAA male athletes who use banned performance enhancing substances. [JOURNAL ARTICLE]
- Drug Alcohol Depend 2013 May 17.