Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

Abstract

In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p's < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p's < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence.

Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment

“…However, they are relatively resistant to handling-induced convulsions, a commonly examined symptom of alcohol abstinence (Crabbe, Young, & Kosobud, 1983; Metten & Crabbe, 1994). When compared to C57BL/6J, the outbred strain Swiss Webster has similar baseline anxiety-like behavior in the EPM and the light/dark box (Crawley et al, 1997; van Gaalen & Steckler, 2000) and similar, low sensitivity to handling-induced convulsions during ethanol withdrawal (Metten & Crabbe, 1994)(Farook et al, 2008; Farook et al, 2007). The DBA2/A inbred strain consumes less alcohol but displays higher handling-induced convulsions scores during alcohol withdrawal when compared to the C57BL/6J strain (Belknap et al, 1993; Yoneyama et al, 2008).…”

“…Such paradigm has been successfully employed in mice to induce handling-induced seizures and anxiety-like behavior during withdrawal (Farook et al, 2008; Farook, Morrell, Lewis, Littleton, & Barron, 2007). Our results indicate that ethanol cessation after a short course of intraperitoneal (ip) injections can produce withdrawal symptoms comparable to those observed after a six week ethanol diet.…”

The Indirect NMDAR Antagonist Acamprosate Induces Postischemic Neurologic Recovery Associated with Sustained Neuroprotection and Neuroregeneration

“…Mice were subjected to 30 minutes of transient focal cerebral ischemia as described below followed by intraperitoneal treatment with either acamprosate (Sigmal-Aldrich, Taufkirchen, Germany; solved in NaCl) or standard saline (control) during reperfusion, at 3, 6, 9, 12, and 24 hours after stroke. Referring to previous studies, [15][16][17][18][19][20] mice received a modified injection protocol with a single intraperitoneal injection of acamprosate at a dose of 400 mg/kg bodyweight (BW). To exclude toxic side effects of acamprosate after high dosage bolus application, analysis of potential weight loss and blood count analysis was performed 1 day before stroke induction as well as on days 7 and 14 after stroke ( Table 1).…”

Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine

“…Mice received a chronic ethanol treatment that has been successfully utilized to induce ethanol withdrawal symptoms upon treatment cessation (Farook et al, 2007). Briefly, mice were injected daily with either 2 g/kg (20% w/v) ethanol or saline for a minimum of 9 days.…”

“…Briefly, mice were injected daily with either 2 g/kg (20% w/v) ethanol or saline for a minimum of 9 days. Both solutions contained 9 mg/kg of the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, Sigma-Aldrich, St Louis, MO) to prolong the half-life of plasma ethanol (Farook et al, 2007;Perez and De Biasi, 2015).…”