- Disulfiram attenuates morphine or methadone withdrawal syndrome in mice. [Journal Article]
- BPBehav Pharmacol 2018 Feb 16
- Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or oth...
Taking opioids is often accompanied by the development of dependence. Unfortunately, treatment of opioid dependence is difficult, particularly because of codependence - for example, on alcohol or other drugs of abuse. In the presented study, we analyzed the potential influence of disulfiram, a drug used to aid the management of alcoholism, on opioid abstinence syndrome, which occurs as a result of opioid withdrawal. Opioid dependence in mice was induced by subcutaneous administration of either morphine or methadone at a dose of 48 mg/kg for 10 consecutive days. To trigger a withdrawal syndrome, the opioid receptor antagonist, naloxone, was administered at a dose of 1 mg/kg (subcutaneous), and the severity of withdrawal signs was assessed individually. Interruption of chronic treatment with morphine or methadone by naloxone has led to the occurrence of opioid abstinence signs such as jumping, paw tremor, wet-dog shakes, diarrhea, teeth chattering, ptosis, and piloerection. Importantly, pretreatment with disulfiram (25, 50, and 100 mg/kg) reduced the intensity of withdrawal signs induced by naloxone in morphine or methadone-treated mice. These findings show the effectiveness of disulfiram in reducing opioid abstinence signs.
- GABA and Glutamate Synaptic Coadaptations to Chronic Ethanol in the Striatum. [Journal Article]
- HEHandb Exp Pharmacol 2018 Feb 20
- Alcohol (ethanol) is a widely used and abused drug with approximately 90% of adults over the age of 18 consuming alcohol at some point in their lifetime. Alcohol exerts its actions through multiple n...
Alcohol (ethanol) is a widely used and abused drug with approximately 90% of adults over the age of 18 consuming alcohol at some point in their lifetime. Alcohol exerts its actions through multiple neurotransmitter systems within the brain, most notably the GABAergic and glutamatergic systems. Alcohol's actions on GABAergic and glutamatergic neurotransmission have been suggested to underlie the acute behavioral effects of ethanol. The striatum is the primary input nucleus of the basal ganglia that plays a role in motor and reward systems. The effect of ethanol on GABAergic and glutamatergic neurotransmission within striatal circuitry has been thought to underlie ethanol taking, seeking, withdrawal and relapse. This chapter reviews the effects of ethanol on GABAergic and glutamatergic transmission, highlighting the dynamic changes in striatal circuitry from acute to chronic exposure and withdrawal.
- Changes in dependent patients with schizophrenia versus non-psychiatric controls during 28-days of cannabis abstinence. [Journal Article]
- DADrug Alcohol Depend 2018 Feb 12; 185:181-188
- CONCLUSIONS: Findings suggest transient tobacco substitution for cannabis in patients with schizophrenia. This provides further support for a strong association between cannabis and tobacco in schizophrenia. Future studies should focus on targeting underlying mechanisms that promote co-use to better address potential changes in concurrent substance use during treatment interventions.
- Traumatic Lingual Hematoma Resulting in Bilateral Temporal Mandibular Joint Dislocations. [Journal Article]
- JEJ Emerg Med 2018 Feb 13
- Lingual hematoma (LH) is a relatively uncommon entity seen after both medical and traumatic etiologies. Regardless of the cause, the feared complication is acute airway obstruction.
Lingual hematoma (LH) is a relatively uncommon entity seen after both medical and traumatic etiologies. Regardless of the cause, the feared complication is acute airway obstruction.
- Neuroadaptations in the dentate gyrus following contextual cued reinstatement of methamphetamine seeking. [Journal Article]
- BSBrain Struct Funct 2018 Feb 13
- Abstinence from unregulated methamphetamine self-administration increases hippocampal dependent, context-driven reinstatement of methamphetamine seeking. The current study tested the hypothesis that ...
Abstinence from unregulated methamphetamine self-administration increases hippocampal dependent, context-driven reinstatement of methamphetamine seeking. The current study tested the hypothesis that alterations in the functional properties of granule cell neurons (GCNs) in the dentate gyrus (DG) of the hippocampus in concert with altered expression of synaptic plasticity-related proteins and ultrastructural changes in the DG are associated with enhanced context-driven methamphetamine-seeking behavior. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naïve (controls) and methamphetamine experienced animals (during acute withdrawal, during abstinence, after extinction and after reinstatement). Spontaneous excitatory postsynaptic currents (sEPSCs) and intrinsic excitability were recorded from GCNs. Reinstatement of methamphetamine seeking increased sEPSC frequency and produced larger amplitude responses in GCNs compared to controls and all other groups. Reinstatement of methamphetamine seeking reduced spiking capability in GCNs compared to controls, and all other groups, as indicated by reduced intrinsic spiking elicited by increasing current injections, membrane resistance and fast after hyperpolarization. In rats that reinstated methamphetamine seeking, these altered electrophysiological properties of GCNs were associated with enhanced expression of Fos, GluN2A subunits and PSD95 and reduced expression of GABAAsubunits in the DG and enhanced expression of synaptic PSD in the molecular layer. The alterations in functional properties of GCNs and plasticity related proteins in the DG paralleled with no changes in structure of microglial cells in the DG. Taken together, our results demonstrate that enhanced reinstatement of methamphetamine seeking results in alterations in intrinsic spiking and spontaneous glutamatergic synaptic transmission in the GCNs and concomitant increases in neuronal activation of GCNs, and expression of GluNs and decreases in GABAAsubunits that may contribute to the altered synaptic connectivity-neuronal circuitry-and activity in the hippocampus, and enhance propensity for relapse.
- Alcohol withdrawal hallucinations in the general population, an epidemiological study. [Journal Article]
- PRPsychiatry Res 2018 Feb 05; 262:129-134
- Hallucinations are sometimes encountered in the course of alcohol withdrawal; however, both the factors predisposing to alcohol withdrawal hallucinations (AWH) and the implications of AWH with respec...
Hallucinations are sometimes encountered in the course of alcohol withdrawal; however, both the factors predisposing to alcohol withdrawal hallucinations (AWH) and the implications of AWH with respect to the mechanisms of hallucinations remain unclear. To clarify these issues, we used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to investigate the demographic correlates, alcohol-use clinical patterns, and psychiatric comorbidities in two groups: drinkers with and without a history of AWH. We estimated the odds ratios for studied factors and used logistic regression analyses to compare the two groups. We found that over 2% of drinkers reported AWH (758 of a sample of 34,533 subjects). Alcohol tolerance and withdrawal seizures were highly associated with AWH, and exposure to alcohol during brain development was associated with a 10-fold increase in AWH compared to exposure during adulthood. African Americans, Native Americans, and unmarried subjects, as well as subjects with lower levels of education and lower levels of income were more likely to experience AWH. Furthermore, those with a history of AWH had higher odds ratios for most psychiatric illnesses than those without such history-yet of anxiety disorders, only panic was associated with AWH. These associations suggest that higher levels of education and of standard of living could protect against AWH; while social isolation, hypervigilance, exposure to alcohol during brain development, and long and severe exposure to alcohol could predispose to AWH.
- Cigarette craving and stressful social interactions: The roles of state and trait social anxiety and smoking to cope. [Journal Article]
- DADrug Alcohol Depend 2018 Feb 05; 185:75-81
- CONCLUSIONS: Smokers high in SA (state and trait) and smoking to cope with symptoms of SA may be at risk for continued smoking and relapse because of the intensity of cravings they experience during stressful social situations.
- An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. [Journal Article]
- AAlcohol 2017 Sep 06; 68:19-35
- Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in pa...
Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.
- Molecular, Neuronal, and Behavioral Effects of Ethanol and Nicotine Interactions. [Journal Article]
- HEHandb Exp Pharmacol 2018 Feb 09
- Ethanol and nicotine can modulate the activity of several neurotransmitter systems and signalling pathways. Interactions between ethanol and nicotine can also occur via common molecular targets inclu...
Ethanol and nicotine can modulate the activity of several neurotransmitter systems and signalling pathways. Interactions between ethanol and nicotine can also occur via common molecular targets including nicotinic acetylcholine receptors (nAChRs). These effects can induce molecular and synaptic adaptations that over time, are consolidated in brain circuits that reinforce drug-seeking behavior, contribute to the development of withdrawal symptoms during abstinence and increase the susceptibility to relapse. This chapter will discuss the acute and chronic effects of ethanol and nicotine within the mesolimbic reward pathway and brain circuits involved in learning, memory, and withdrawal. Individual and common molecular targets of ethanol and nicotine within these circuits are also discussed. Finally, we review studies that have identified potential molecular and neuronal processes underlying the high incidence of ethanol and nicotine co-use that may contribute to the development of ethanol and nicotine co-addiction.
New Search Next
- Effects of Alcohol on the Brain in Cirrhosis: Beyond Hepatic Encephalopathy. [Journal Article]
- ACAlcohol Clin Exp Res 2018 Feb 08
- Recent advances have led to a greater understanding of how alcohol alters the brain, both in acute stages (intoxication and alcohol withdrawal) and in chronic misuse. This review focuses on the curre...
Recent advances have led to a greater understanding of how alcohol alters the brain, both in acute stages (intoxication and alcohol withdrawal) and in chronic misuse. This review focuses on the current understanding of how alcohol affects the brain in cirrhosis patients with and without hepatic encephalopathy. Chronic alcohol use is associated with nutritional deficiencies, dementia, cirrhosis, and decompensating events such as hepatic encephalopathy. Direct toxicity on brain tissue, induction of neuro-inflammation, and alcohol's alterations of the gut microbiome are possible mechanisms for the clinical features of hepatic encephalopathy associated with alcohol use. Acute management of the alcoholic cirrhosis patient with altered mental status should focus on ruling out other causes, best intensive care, and use of gut-based therapies such as lactulose and rifaximin. Long term management centers on optimizing treatment of concurrent mood disorders, nutritional support, and medical management of complications associated with cirrhosis. Future studies are needed to clarify mechanisms of brain injury in concomitant alcohol misuse and HE in addition to designing treatment interventions in order to improve outcomes in these patients. This article is protected by copyright. All rights reserved.