Baclofen Blocks Expression and Sensitization of Anxiety‐Like Behavior in an Animal Model of Repeated Stress and Ethanol Withdrawal

Knapp, Darin J.; Overstreet, David H.; Breese, George R.

doi:10.1111/j.1530-0277.2007.00342.x

Cited by 77 publications

(60 citation statements)

References 73 publications

(120 reference statements)

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“…Withdrawal symptoms after repeated administration of GHB have been described in baboons (Weerts et al 2005), rats (Bania et al 2003) and humans (LeTourneau et al 2008) and the present data extend these findings to suggest a withdrawal syndrome after ten daily injections of 500 mg/kg GHB to rats. The increased social anxiety seen after abrupt discontinuation of GHB treatment is reminiscent of that seen in rats undergoing either ethanol (Knapp et al 2007) or benzodiazepine (File et al 1991) withdrawal, and consistent with there being some similarity in the neuroadaptations caused by these compounds on brain GABAergic systems. Interestingly, this withdrawal effect was not seen in rats given the MDMA/GHB combination, suggesting an amelioration of acute GHB withdrawal when coadministered with MDMA.…”

Section: Discussionmentioning

confidence: 65%

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

et al. 2010

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Section: Discussionmentioning

confidence: 65%

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

et al. 2010

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“…Furthermore, numerous reports have shown that withdrawal from chronic intermittent EtOH exposure results in pronounced increases in anxiety-like behaviors (for review see Kliethermes, 2005;McCool et al, 2010). In addition, cycles of chronic stress can substitute for cycles of chronic intermittent EtOH exposure (Knapp et al, 2007). Therefore, it also seems possible that chronic EtOH exposure may disrupt inhibitory effects of NE in the BLA and thus contribute to the progressive increase in anxiety associated with alcohol abuse disorders.…”

Section: ␤1-ars Mediate Etoh Enhancement Of Lpcs Gabaergic Synapses 457mentioning

confidence: 99%

β1-Adrenoceptor Activation Is Required for Ethanol Enhancement of Lateral Paracapsular GABAergic Synapses in the Rat Basolateral Amygdala

Silberman

Ariwodola

Weiner

2012

J Pharmacol Exp Ther

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Ethanol (EtOH) potentiation of GABAergic neurotransmission in the basolateral amygdala (BLA) may contribute to the acute anxiolytic effects of this drug. Previous studies have shown that BLA pyramidal neurons receive GABAergic input from two distinct sources: local interneurons and a cluster of GABAergic cells termed lateral paracapsular (LPCS) interneurons. It is noteworthy that whereas EtOH enhances local GABAergic synapses via a presynaptic increase in GABA release, EtOH potentiation of LPCS inhibition is mediated via a distinct mechanism that requires adrenoceptor (AR) activation. Here, we sought to further characterize the interaction between the AR system and EtOH enhancement of LPCS GABAergic synapses by using in vitro electrophysiology techniques in male SpragueDawley rats. Exogenous norepinephrine (NE) enhanced LPCSevoked inhibitory postsynaptic currents (eIPSCs) via the activation of ␤-ARs, because this effect was blocked by propranolol. EtOH potentiation of LPCS eIPSCs was also blocked by propranolol and significantly reduced by NE pretreatment, suggesting that NE and EtOH may enhance LPCS inhibition via a common mechanism. EtOH enhancement of LPCS eIPSCs was significantly reduced by a selective ␤1-, but not ␤2-or ␤3-, AR antagonist, and both EtOH and NE potentiation of LPCS IPSCs was blocked by postsynaptic disruption of cAMP signaling. These data suggest that EtOH enhances LPCS synapses via a postsynaptic ␤1-AR, cAMP-dependent cascade. Because enhancement of LPCS inhibition can reduce anxiety-like behaviors, these findings shed light on a novel mechanism that may play a role in some of the anxiolytic effects of EtOH that are thought to contribute to the development and progression of alcoholism.

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“…Furthermore, administration of baclofen has been reported to inhibit the severity of the alcohol withdrawal syndrome (AWS), including anxiety-related behaviors, tremors, and seizures in rats made physically dependent on alcohol Knapp et al, 2007). Different lines of experimental evidence suggest that mesolimbic DA neurons are involved in the mediation of alcohol intake and reinforcement (Weiss and Porrino, 2002;Melis et al, 2005).…”

Section: Baclofenmentioning

confidence: 99%

“…Preclinical data showed that baclofen reduces the severity of AWS in rats made physically dependent on alcohol Knapp et al, 2007). On the basis of preliminary promising results in humans (Addolorato et al, 2002), a randomized study compared baclofen (10 mg t.id.…”

Section: Baclofenmentioning

confidence: 99%

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

Addolorato

Leggio

Hopf

et al. 2011

Neuropsychopharmacol

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Drug addiction represents a major social problem where addicts and alcoholics continue to seek and take drugs despite adverse social, personal, emotional, and legal consequences. A number of pharmacological compounds have been tested in human addicts with the goal of reducing the level or frequency of intake, but these pharmacotherapies have often been of only moderate efficacy or act in a sub-population of humans. Thus, there is a tremendous need for new therapeutic interventions to treat addiction. Here, we review recent interesting studies focusing on gamma-aminobutyric acid receptors, voltage-gated ion channels, and transcranial magnetic stimulation. Some of these treatments show considerable promise to reduce addictive behaviors, or the early clinical studies or pre-clinical rationale suggest that a promising avenue could be developed. Thus, it is likely that within a decade or so, we could have important new and effective treatments to achieve the goal of reducing the burden of human addiction and alcoholism.

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Baclofen Blocks Expression and Sensitization of Anxiety‐Like Behavior in an Animal Model of Repeated Stress and Ethanol Withdrawal

Cited by 77 publications

References 73 publications

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

β1-Adrenoceptor Activation Is Required for Ethanol Enhancement of Lateral Paracapsular GABAergic Synapses in the Rat Basolateral Amygdala

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

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