Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates

Carden, W. Breckinridge; Alexander, Georgia M.; Friedman, David P.; Daunais, James B.; Grant, Kathleen A.; Mu, Jian; Godwin, Dwayne W.

doi:10.1016/j.brainres.2006.02.135

Cited by 27 publications

(27 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Now these tissues and associated bioinformatics are widely available to the larger alcohol research community through the interactive MATRR website. Since its inception, the MATRR has contributed resources that have been cited in 70 peer-reviewed publications, including reports of the functional (Ariwodola et al, 2003; Budygin et al, 2003; Floyd et al, 2004; Alexander et al, 2006; Carden et al, 2006; Anderson et al, 2007; Cuzon-Carlson et al, 2012; Welsh et al, 2011), genomic (Hemby et al, 2006; Acosta et al, 2009; Burnett et al, 2012), proteomic (Freeman et al, 2006, 2010, 2011), biochemical (Ivester et al, 2003; 2007; Lebold et al, 2010) and cardiac (Cheng et al, 2010) consequences of long-term, excessive ethanol consumption. The pathophysiological effects of chronic EtOH on the hypothalamic-pituitary-adrenal axis have also been well-characterized (Morrow et al, 2006; Porcu et al, 2006a, b, 2010; Ferguson et al, 2012; Helms et al, 2012a, b, c, 2013).…”

Section: Resultsmentioning

confidence: 99%

Monkey Alcohol Tissue Research Resource: Banking Tissues for Alcohol Research

Daunais

Davenport

Helms

et al. 2014

Alcohol Clin Exp Res

Self Cite

View full text Add to dashboard Cite

Background An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is co-morbid with damage to major organs including heart, lungs, liver, pancreas and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of EtOH and they metabolize it more rapidly than primates. Methods The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates (NHPs), specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent/day) over long periods of time (12–30 months) with concomitant pathological changes in endocrine, hepatic and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the ethanol-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. Results The MATRR is a unique post-mortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer ethanol using a standardized experimental paradigm to the broader alcohol research community. Conclusions This resource provides a translational platform from which we can better understand the disease processes associated with alcoholism.

show abstract

Section: Resultsmentioning

confidence: 99%

Monkey Alcohol Tissue Research Resource: Banking Tissues for Alcohol Research

Daunais

Davenport

Helms

et al. 2014

Alcohol Clin Exp Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our prior studies have shown significant effects of ethanol exposure and withdrawal on the physiology of T-type channels (Carden et al, 2006; Graef et al, 2011; Mu, Carden, Kurukulasuriya, Alexander, & Godwin, 2003; Shan, Hammarback, & Godwin, 2013; Wiggins, Graef, Huitt, & Godwin, 2013). Our current study extends these findings with the following observations: 1) ethanol withdrawal increased the incidence of seizure in DBA/2J mice; 2) ETX decreased ethanol withdrawal-induced seizures evident by reduced electrographical and behavioral measures of seizure; 3) ETX treatment rescued mice from seizures prior to withdrawal treatment.…”

Section: Discussionmentioning

confidence: 99%

Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

Riegle

Masicampo

Caulder

et al. 2014

Alcohol

Self Cite

View full text Add to dashboard Cite

Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power reduction in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures.

show abstract

“…Using monkeys treated like our CI group, a recent study (44) found plasticity in I T with chronic ethanol in the lateral geniculate nucleus (LGN). Although the direction of plasticity was opposite to our finding in the IO, low doses of ethanol augmented I T in LGN neurons (45), and the monkeys in that study (44) consumed less ethanol per day than did our CI group. The different outcomes could be caused by different Ca V 3.1 splice variants (46).…”

Section: Discussionmentioning

confidence: 99%

Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence

Welsh¹,

Han

Rossi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The brain adapts to chronic ethanol intoxication by altering synaptic and ion-channel function to increase excitability, a homeostatic counterbalance to inhibition by alcohol. Delirium tremens occurs when those adaptations are unmasked during withdrawal, but little is known about whether the primate brain returns to normal with repeated bouts of ethanol abuse and abstinence. Here, we show a form of bidirectional plasticity of pacemaking currents induced by chronic heavy drinking within the inferior olive of cynomolgus monkeys. Intracellular recordings of inferior olive neurons demonstrated that ethanol inhibited the tail current triggered by release from hyperpolarization (I tail ). Both the slow deactivation of hyperpolarization-activated cyclic nucleotide-gated channels conducting the hyperpolarization-activated inward current and the activation of Ca v 3.1 channels conducting the T-type calcium current (I T ) contributed to I tail , but ethanol inhibited only the I T component of I tail . Recordings of inferior olive neurons obtained from chronically intoxicated monkeys revealed a significant up-regulation in I tail that was induced by 1 y of daily ethanol self-administration. The up-regulation was caused by a specific increase in I T which (i) greatly increased neurons' susceptibility for rebound excitation following hyperpolarization and (ii) may have accounted for intention tremors observed during ethanol withdrawal. In another set of monkeys, sustained abstinence produced the opposite effects: (i) a reduction in rebound excitability and (ii) a down-regulation of I tail caused by the down-regulation of both the hyperpolarizationactivated inward current and I T . Bidirectional plasticity of two hyperpolarization-sensitive currents following chronic ethanol abuse and abstinence may underlie persistent brain dysfunction in primates and be a target for therapy.A cute ethanol withdrawal affects millions of people and can require management of a syndrome that consists of dysautonomia, seizures, cognitive disturbance, and tremor (1, 2). It generally is agreed that the washout of ethanol from the brain during acute withdrawal unmasks the physiological adaptations of neurons that allow them to function while they are bathed in ethanol (3, 4). It sometimes is assumed that once the symptoms of acute withdrawal are managed, long-term abstinence from ethanol gradually restores the brain to a preethanol state. Nevertheless, an alcoholic's drive to ingest ethanol can persist even after months or years of abstinence, and alcoholics can undergo multiple abstinences from alcohol in their lifetime.We tested the hypothesis that adaptations in the intrinsic electrical properties of inferior olive (IO) neurons are changed by chronic ethanol intake and by subsequent abstinence. We used patch-clamp recordings of IO neurons in acutely prepared brainstem slices from chronically intoxicated cynomolgus monkeys (5-7) to examine changes in intrinsic electrical properties with ethanol intake and repeated abstinences. We addressed two qu...

show abstract

Chronic ethanol drinking reduces native T-type calcium current in the thalamus of nonhuman primates

Cited by 27 publications

References 39 publications

Monkey Alcohol Tissue Research Resource: Banking Tissues for Alcohol Research

Monkey Alcohol Tissue Research Resource: Banking Tissues for Alcohol Research

Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

Bidirectional plasticity in the primate inferior olive induced by chronic ethanol intoxication and sustained abstinence

Contact Info

Product

Resources

About