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Murphy, James M.; Stewart, Robert B.; Bell, Richard L.; Badia-Elder, Nancy E.; Carr, Lucinda G.; McBride, William J.; Lumeng, Lawrence; Li, Ting Kai

doi:10.1023/a:1020266306135

Cited by 303 publications

(98 citation statements)

References 183 publications

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“…Several animal models have been developed to study the genetic and neurobiological basis of alcoholism (McBride and Li, 1998). One such animal model is the selectively bred alcohol-preferring (P) and - nonpreferring (NP) rats who display higher and lower alcohol preference, respectively (Li et al, 1993; Murphy et al, 2002). In addition, P rats also display heightened anxiety-like behaviors as compared to NP rats (Stewart et al, 1993; Pandey et al, 2005; Gilpin et al, 2011; Moonat et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours

Sakharkar

Zhang

Tang

et al. 2014

Int. J. Neuropsychopharm.

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Recent studies have demonstrated the involvement of epigenetic mechanisms in psychiatric disorders including alcoholism. Here, we investigated the effects of histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) on amygdaloid HDAC-induced histone deacetylation and neuropeptide Y (NPY) expression and on anxiety-like and alcohol-drinking behaviors in alcohol-preferring (P) and - nonpreferring (NP) rats. It was found that P rats displayed higher anxiety-like and alcohol-drinking behaviors, higher amygdaloid nuclear, but not cytosolic, HDAC activity which was associated with increased HDAC2 protein levels and deficits in histone acetylation and NPY expression in the central (CeA) and medial nucleus of amygdala (MeA), as compared to NP rats. TSA treatment attenuated the anxiety-like and alcohol-drinking behaviors, with concomitant reductions in amygdaloid nuclear, but not cytosolic HDAC activity, and HDAC2, but not HDAC4, protein levels in the CeA and MeA of P rats, without effect in NP rats. TSA treatment also increased global histone acetylation (H3-K9 and H4-K8) and NPY expression in the CeA and MeA of P, but not in NP rats. Histone H3 acetylation within the NPY promoter was also innately lower in the amygdala of P rats compared with NP rats; which was normalized by TSA treatment. Voluntary ethanol intake in P, but not NP rats, produced anxiolytic effects and decreased the HDAC2 levels and increased histone acetylation in the CeA and MeA. These results suggest that higher HDAC2 expression-related deficits in histone acetylation may be involved in lower NPY expression in the amygdala of P rats, and operative in controlling anxiety-like and alcohol-drinking behaviors.

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Section: Introductionmentioning

confidence: 99%

Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours

Sakharkar

Zhang

Tang

et al. 2014

Int. J. Neuropsychopharm.

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“…Alcohol preferring rats (P rats) provide a validated preclinical rodent model of AUD (Murphy et al, 2002). These rodents were selectively bred for alcohol preference and model at risk human populations for excessive drinking, such as individuals with a family history of alcoholism (Froehlich, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tolcapone Suppresses Ethanol Intake in Alcohol‐Preferring Rats Performing a Novel Cued Access Protocol

McCane

Czachowski

Lapish

2014

Alcoholism Clin & Exp Res

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Background Dopamine (DA) has been shown to play a central role in regulating motivated behavior and encoding reward. Chronic drug abuse elicits a state of hypodopaminergia in the mesocorticolimbic (MCL) system in both humans and preclinical rodent models of addiction, including those modeling alcohol use disorders (AUD). Methods Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the COMT inhibitor Tolcapone was used as a means to amplify cortical DA efflux and drinking behaviors were then assessed. Sucrose and ethanol consumption were measured in P and Wistar rats in both a free choice drinking protocol and a novel cued access protocol. Results Tolcapone attenuated the consumption of ethanol, and to a lesser extent sucrose, in P rats in the cued access protocol, while no effect was observed in the free choice drinking protocol. Tolcapone also decreased ethanol consumption in high drinking Wistar rats. A follow-up experiment using the DA agonist D-amphetamine (AMPH) showed no change in ethanol consumption. Conclusions Collectively, these data suggest that COMT inhibitors may be capable of alleviating the extremely motivating or salient nature of stimuli associated with alcohol. The hypothesis is put forth that the relative specificity of Tolcapone for cortical DA systems may mediate the suppression of the high seeking/drinking phenotype.

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“…Oral ethanol consumption is widely used to investigate the genetic and neurobiological basis for high ethanol preference (Murphy et al 2002; Tabakoff et al 2008). The quantity of ethanol consumption is usually measured using the two-bottle choice test; animals are given a choice of either ethanol or water in their home cages and ethanol preference is determined based on the intake of ethanol and water (Green and Grahame 2008; Yoneyama et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of phosphodiesterase-4 decreases ethanol intake in mice

Chen

et al. 2011

Psychopharmacology

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Rationale Cyclic AMP (cAMP)-protein kinase A (PKA) signaling has been implicated in the regulation of ethanol consumption. Phosphodiesterase-4 (PDE4) specifically hydrolyzes cAMP and plays a critical role in controlling intracellular cAMP levels in the brain. However, the role of PDE4 in ethanol consumption remains unknown. Objective To examine whether PDE4 was involved in regulating ethanol intake. Methods The two-bottle choice paradigm was used to assess intake of ethanol, sucrose, and quinine in C57BL/6J mice treated with the selective PDE4 inhibitor rolipram or Ro 20-1724; locomotor activity was also monitored using the open-field test in mice treated with rolipram. Results Administration (i.p.) of either rolipram (0.25 and 0.5 mg/kg) or Ro 20-1724 (10 mg/kg) reduced ethanol intake and preference by 60-80%, but did not alter total fluid intake. In contrast, rolipram even at the higher dose of 0.5 mg/kg was not able to affect intake of sucrose or quinine, alcohol-induced sedation, or blood ethanol elimination. At 0.5 mg/kg, rolipram did decrease locomotor activity, but the effect only lasted for approximately 40 min, which did not likely affect behavior of ethanol drinking. Conclusions These results suggest that PDE4 is a novel target for drugs that reduce ethanol intake; PDE4 inhibitors may be used for treatment of alcohol dependence.

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Cited by 303 publications

References 183 publications

Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours

Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours

Tolcapone Suppresses Ethanol Intake in Alcohol‐Preferring Rats Performing a Novel Cued Access Protocol

Inhibition of phosphodiesterase-4 decreases ethanol intake in mice

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