Effects of chronic ethanol administration and ethanol withdrawal on cyclic guanosine 3′,5′-monophosphate (cGMP) levels in the rat brain

Uzbay, I.T.; Çelik, Turgay; Aydın, Ahmet; Kayır, Hakan; Tokgöz, Serhat; Bilgi, Cumhur

doi:10.1016/j.drugalcdep.2003.11.011

Cited by 18 publications

(13 citation statements)

References 23 publications

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“…Consistent with the previous findings on the same model [23,25,[29][30][31] the present data demonstrated that daily ethanol consumption above 11 g/kg for 15 consecutive days produced physical dependence in rats. At doses of 25, 50, and 100 mg/kg, HPE blocked both locomotor hyperactivity and stereotyped behaviors especially at 2 and 6 h of ethanol withdrawal.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, it attenuated the incidence of tremor in ethanol-dependent rats at 4 h of ethanol withdrawal. The rate of audiogenic seizures observed in the present study was also very similar to those of previous studies that used the same animal model [25,[30][31][32][33]. Latency of the audiogenic seizures was also prolonged significantly by HPE (25 and 50 mg/kg) treatment.…”

Section: Discussionsupporting

confidence: 90%

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Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats

Coşkun

Uzbay

Öztürk

et al. 2006

Fundamemntal Clinical Pharma

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The effects of Hypericum perforatum (St John's wort) on ethanol withdrawal syndrome have been investigated in ethanol-dependent rats. Adult male Wistar rats were subjects. Ethanol (7.2% v/v) was given to rats by a liquid diet for 15 days. Hypericum perforatum extract (HPE) (25-200 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After second, fourth and sixth hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behavior and tremors were recorded or rated. A second series of injections was given at 6 h after the first one, and subjects were then tested for audiogenic seizures. HPE (25-200 mg/kg) produced some dose-dependent and significant inhibitory effects on locomotor hyperactivity at second and sixth hour of ethanol withdrawal. In addition, it significantly reduced the number of stereotyped behaviors at the same dose range. HPE (50 and 100 mg/kg) produced some significant inhibitory effects on tremor and audiogenic seizures during withdrawal period. These results suggest that HPE has some beneficial effects on ethanol withdrawal syndrome in rats.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats

Coşkun

Uzbay

Öztürk

et al. 2006

Fundamemntal Clinical Pharma

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“…Consumption of an alcohol-containing liquid diet for at least 2 weeks increased cGMP levels in the cortex, striatum, and hippocampus, with cortical and striatal levels normalizing within 24 h of diet removal (Uzbay et al, 2004). Alcohol induction of cGMP likely contributes to regulation of alcohol-related behaviors, as deletion of the gene encoding PKG type II reduced alcohol’s sedative effects and potentiated alcohol intake, without affecting alcohol clearance or consumption of sweet solutions (Werner et al, 2004).…”

Section: Cyclic Nucleotide Signaling Regulates Molecular and Behaviormentioning

confidence: 99%

Phosphodiesterase regulation of alcohol drinking in rodents

Logrip

2015

Alcohol

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Alcohol use disorders are chronically relapsing conditions characterized by persistent drinking despite the negative impact on one’s life. The difficulty of achieving and maintaining sobriety suggests that current treatment options fail to fully address the underlying causes of alcohol use disorders, and thus identifying additional pathways controlling alcohol consumption may uncover novel targets for medication development to improve treatment options. One family of proteins recently implicated in the regulation of alcohol consumption is the cyclic nucleotide phosphodiesterases (PDEs). As an integral component in the regulation of the second messengers cyclic AMP and cyclic GMP, and thus their cognate signaling pathways, PDEs present intriguing targets for pharmacotherapies to combat alcohol use disorders. As activation of cAMP/cGMP-dependent signaling cascades can dampen alcohol intake, PDE inhibitors may provide a novel target for reducing excessive alcohol consumption, as has been proposed for PDE4 and PDE10A. This review highlights preclinical literature demonstrating the involvement of cyclic nucleotide-dependent signaling in neuronal and behavioral responses to alcohol, as well as detailing the capacity of various PDE inhibitors to modulate alcohol intake. Together these data provide a framework for evaluating the potential utility of PDE inhibitors as novel treatments for alcohol use disorders.

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“…Dopaminergic transmission is enhanced during AWS (high plasma homovallinic acid has been observed in patients with delirium tremens21) and may play a role in hallucination formation;22 23 increased dopamine receptor-binding density (D2 in the dorsal striatum and D1 in the amygdala) has also been observed 24. The potential importance of the amygdala and the striatum in the pathophysiology of alcohol withdrawal has also been suggested by persisting high levels of cyclic guanosine 3′,5′-monophosphate (cGMP) in these regions in rats 25. Neurons in the deep layers of the superior colliculus are also an important part of the neural network that initiates ethanol withdrawal seizures 26.…”

Section: Pathophysiologymentioning

confidence: 99%

The alcohol withdrawal syndrome

McKeon

Frye

Delanty

2008

Journal of Neurology, Neurosurgery & Psychiatry

225

156

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The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

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Effects of chronic ethanol administration and ethanol withdrawal on cyclic guanosine 3′,5′-monophosphate (cGMP) levels in the rat brain

Cited by 18 publications

References 23 publications

Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats

Attenuation of ethanol withdrawal syndrome by extract of Hypericum perforatum in Wistar rats

Phosphodiesterase regulation of alcohol drinking in rodents

The alcohol withdrawal syndrome

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