- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Naltrexone is an opioid antagonist used to treat alcohol use disorder and opioid dependence. It was developed in 1963 and patented in 1967. In 1984, naltrexone was approved for medical use in the Uni...
Naltrexone is an opioid antagonist used to treat alcohol use disorder and opioid dependence. It was developed in 1963 and patented in 1967. In 1984, naltrexone was approved for medical use in the United States. While experimenting with rats at the University of Pennsylvania, Dr. Joseph Volpicelli first recognized naltrexone's potential to treat alcoholism. The World Health Organization (WHO) estimates that over 75 million people had alcohol abuse or dependence worldwide. Naltrexone is a mu-opioid antagonist. It is FDA-approved for alcohol abuse and opioid dependence treatment. Off-label use includes treatment of cholestatic pruritus in adults. Researchers are studying its use in patients with stimulant addiction, particularly for patients with polydrug dependence on opioids, heroin, and amphetamine.
- Implication of nigral dopaminergic lesion and repeated L-dopa exposure in neuropsychiatric symptoms of Parkinson's disease. [Journal Article]
- BBBehav Brain Res 2018 Dec 03
- This study aims to investigate the contribution of nigral dopaminergic (DA) cell loss, repeated exposure to DA medication and the combination of both to the development of neuropsychiatric symptoms o...
This study aims to investigate the contribution of nigral dopaminergic (DA) cell loss, repeated exposure to DA medication and the combination of both to the development of neuropsychiatric symptoms observed in Parkinson's disease (PD). A bilateral 6-OHDA lesion of the substantia nigra pars compacta (SNc) was performed in rats. A set of animals was repeatedly administered with L-dopa (20 mg/kg/day) and benserazide (5 mg/kg/day) over 10 days starting from day 11 post-lesion. Behavioural testing was performed in week 3 post-lesion: novel object recognition (NOR), elevated plus maze (EPM) social interaction (SI) tests, and amphetamine-induced hyperlocomotion (AIH). Immunohistochemical analysis revealed a significant partial lesion (48%) in 6-OHDA versus sham rats. This lesion was not associated with motor impairment. However, lesioned rats displayed a significant deficit in the NOR, which was reversed by acute treatment with L-dopa/benserazide (12.5 mg/kg and 15 mg/kg respectively). Lesioned rats also displayed a deficit in the EPM which was not reversed by acute treatment with L-dopa. No difference was observed in the SI test or in the AIH assay. In all assays, no effect of chronic L-dopa exposure was observed. This study provides new insights into the neuropathophysiology associated with neuropsychiatric symptoms of PD. Our data strongly emphasises a not previously clearly identified critical role in cognition for the SNc. The results suggest that DA pathways were less directly involved in lesion-induced anxiety-like behaviour. We did not report any effect of chronic L-dopa exposure in the context of partial nigral cell loss.
- Behavioral effects of psychostimulants in mutant mice with cell-type specific deletion of CB2 cannabinoid receptors in dopamine neurons. [Journal Article]
- BBBehav Brain Res 2018 Nov 30
- Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic...
Activation of the endocannabinoid system modulate dopaminergic pathways that are involved in the effects of psychostimulants including amphetamine, cocaine, nicotine and other drugs of abuse. Genetic deletion or pharmacological activation of CB2 cannabinoid receptor is involved in the modulation of the effects of psychostimulants and their rewarding properties. Here we report on the behavioral effects of psychostimulants in DAT-Cnr2 conditional knockout (cKO) mice with selective deletion of type 2 cannabinoid receptors in dopamine neurons. There was enhanced psychostimulant induced hyperactivity in DAT-Cnr2 cKO mice, but the psychostimulant-induced sensitization was absent in DAT-Cnr2 cKO compared to the WT mice. Intriguingly lower doses of amphetamine reduced locomotor activity of the DAT-Cnr2 cKO mice. While cocaine, amphetamine and methamphetamine produced robust conditioned place preference (CPP) in both DAT-Cnr2 cKO and WT mice, nicotine at the dose used induced CPP only in the WT but not in the DAT-Cn2 cKO mice. However pre-treatment with the CB2R selective agonist JWH133, blocked cocaine and nicotine induced CPP in the WT mice. The deletion of CB2Rs in dopamine neurons modified the levels of tyrosine hydroxylase, and reduced the expression of dopamine transporter gene expression in DAT-Cnr2 cKO midbrain region. Taken together, our data suggest that CB2Rs play a role in the modulation of dopamine-related effects of psychostimulants and could be exploited as therapeutic target in psychostimulant addiction and other psychiatric disorders associated with dopamine dysregulation.
- Reduced Efficacy of d-Amphetamine and 3,4-Methylenedioxymethamphetamine in Inducing Hyperactivity in Mice Lacking the Postsynaptic Scaffolding Protein SHANK1. [Journal Article]
- FMFront Mol Neurosci 2018; 11:419
- Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectru...
Genetic defects in the three SH3 and multiple ankyrin repeat domains (SHANK) genes (SHANK1, SHANK2, and SHANK3) are associated with multiple major neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BPD). Psychostimulant-induced hyperactivity is a commonly applied paradigm to assess behavioral phenotypes related to BPD and considered to be the gold standard for modeling mania-like elevated drive in mouse models. Therefore, the goal of our present study was to test whether Shank1 plays a role in the behavioral effects of psychostimulants and whether this is associated with genotype-dependent neurochemical alterations. To this aim, male and female null mutant Shank1-/- mice were treated with d-amphetamine (AMPH; 2.5 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA, commonly known as ecstasy; 20 mg/kg), and psychostimulant-induced hyperactivity was compared to heterozygous Shank1+/- and wildtype Shank1+/+ littermate controls. Results show that Shank1-/- mice display reduced psychostimulant-induced hyperactivity, although psychostimulants robustly stimulated locomotor activity in littermate controls. Shank1 deletion effects emerged throughout development, were particularly prominent in adulthood, and seen in response to both psychostimulants, i.e., AMPH and MDMA. Specifically, while AMPH-induced hyperactivity was reduced but still detectable in Shank1-/- mice, MDMA-induced hyperactivity was robustly blocked and completely absent in Shank1-/- mice. Reduced efficacy of psychostimulants to stimulate hyperactivity in Shank1-/- mice might be associated with alterations in the neurochemical architecture in prefrontal cortex, nucleus accumbens, and hypothalamus. Our observation that psychostimulant-induced hyperactivity is reduced rather than enhanced in Shank1-/- mice clearly speaks against a behavioral phenotype with relevance to BPD. Lack of BPD-like phenotype is consistent with currently available human data linking mutations in SHANK2 and SHANK3 but not SHANK1 to BPD.
- Neurobiological and immunogenetic aspects of narcolepsy: Implications for pharmacotherapy. [Review]
- SMSleep Med Rev 2018 Nov 08; 43:23-36
- Excessive daytime sleepiness (EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons. Although only a few drugs have recei...
Excessive daytime sleepiness (EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons. Although only a few drugs have received regulatory approval for narcolepsy to date, treatment involves diverse medications that affect multiple biochemical targets and neural circuits. Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H3-receptor inverse agonist/antagonist pitolisant. Enhanced catecholamine availability and regulation of locus coeruleus (LC) norepinephrine (NE) neuron activity is likely central to the therapeutic activity of most of these compounds. LC NE neurons are integral to sleep/wake regulation and muscle tone; reduced excitatory input to the LC due to compromise of Hcrt/orexin neurons (likely due to autoimmune factors) results in LC NE dysregulation and contributes to narcolepsy/cataplexy symptoms. Agents that increase catecholamines and/or LC activity may mitigate EDS and cataplexy by elevating NE regulation of GABAergic inputs from the amygdala. Consequently, novel medications and treatment strategies aimed at preserving and/or modulating Hcrt/orexin-LC circuit integrity are warranted in narcolepsy/cataplexy.
- Open-field PET: Simultaneous brain functional imaging and behavioural response measurements in freely moving small animals. [Journal Article]
- NNeuroimage 2018 Nov 28
- A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli....
A comprehensive understanding of how the brain responds to a changing environment requires techniques capable of recording functional outputs at the whole-brain level in response to external stimuli. Positron emission tomography (PET) is an exquisitely sensitive technique for imaging brain function but the need for anaesthesia to avoid motion artefacts precludes concurrent behavioural response studies. Here, we report a technique that combines motion-compensated PET with a robotically-controlled animal enclosure to enable simultaneous brain imaging and behavioural recordings in unrestrained small animals. The technique was used to measure in vivo displacement of [11C]raclopride from dopamine D2 receptors (D2R) concurrently with changes in the behaviour of awake, freely moving rats following administration of unlabelled raclopride or amphetamine. The timing and magnitude of [11C]raclopride displacement from D2R were reliably estimated and, in the case of amphetamine, these changes coincided with a marked increase in stereotyped behaviours and hyper-locomotion. The technique, therefore, allows simultaneous measurement of changes in brain function and behavioural responses to external stimuli in conscious unrestrained animals, giving rise to important applications in behavioural neuroscience.
- Bilateral Basal Ganglia Necrosis Secondary to Methamphetamine. [Journal Article]
- MDMov Disord Clin Pract 2018 Sep-Oct; 5(5):555-556
- Molecular Docking Studies of Methamphetamine and Amphetamine-Related Derivatives as an Inhibitor against dopamine Receptor. [Journal Article]
- CCCurr Comput Aided Drug Des 2018 Dec 04
- The catecholamines such as dopamine, norepinephrine, and epinephrine are neurotransmitters that regulate different physiological functions of the central nervous system. Some evidence suggest that th...
The catecholamines such as dopamine, norepinephrine, and epinephrine are neurotransmitters that regulate different physiological functions of the central nervous system. Some evidence suggest that the degeneration of dopamine neurons in the substantia nigra contributes in Parkinson's disease (PD), which is a neurodegenerative disorder and it is responsible for the major symptoms of PD. It is suggested that replenishment of striatal dopamine through the oral administration of the dopamine precursor, levodopa, can compensate the lack of endogenously produced dopamine. Some studies have shown the competitive inhibition of dopamine receptor such as methamphetamine, and other amphetamine-related derivatives, which block dopamine receptor activity to uptake dopamine.
- Boosting treatment stabilization in patients of amphetamine-type stimulant use disorder. [Journal Article]
- IJInt J Drug Policy 2018 Nov 30; 64:1-4
- CONCLUSIONS: The mandatory treatment modality boosted treatment stabilization for patients of amphetamine-type stimulant use disorder. The major benefit of using the monitoring model is the ability to monitor boosting effects of stabilization. Results supported the effectiveness of this mandatory treatment modality and can be implemented in deferred-prosecution based treatment modality.
New Search Next
- Wastewater-based monitoring of illicit drug consumption in Istanbul: Preliminary results from two districts. [Journal Article]
- STSci Total Environ 2018 Nov 24; 656:231-238
- Wastewater-based epidemiology is a well-established and complementary approach for monitoring illicit drug use in the general population. In this study, amphetamine (AMP), methamphetamine (METH), 3,4...
Wastewater-based epidemiology is a well-established and complementary approach for monitoring illicit drug use in the general population. In this study, amphetamine (AMP), methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), cocaine (COC) (from benzoylecgonine), and cannabis (from THC-COOH) consumption levels were investigated for the first time in Turkey (Istanbul). A solid-phase extraction method was applied to influent wastewater samples collected from two districts, Beyoglu and Catalca. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was conducted with electrospray ionization in positive mode. Calibration curves were acquired in linear form with >0.999 correlation coefficients. Limit of detection levels were measured as 0.91-151 ng/L, and limit of quantitation levels were in the range of 3 to 500 ng/L. Solid-phase extraction recovery and repeatability experiments were achieved by spiking the mix solution to different concentrations (50, 250, 750 ng/L) in 50 mL tap water and wastewater (500, 1000 ng/L) samples in six replicates. The method was optimized, and recoveries were found to be over 80% for all six substances with up to 11.9% relative standard deviation. According to the real sample results, cannabis was found to be the most abused illicit substance among the analytes. The mean consumptions of the two districts, including seven consecutive days for AMP, METH, MDMA, COC, and cannabis, were found to be 27.2, 322, 331, 385, and 1224 mg/day/1000 inhabitants, respectively. In this presented study, all targeted compounds were analyzed simultaneously with the same analytical conditions. To the best of our knowledge, this report is the first to present illicit drug consumption data from Istanbul.