Acute effects of Naltrexone and GBR 12909 on ethanol drinking-in-the-dark in C57BL/6J mice

Abstract

The DID model demonstrates predictive validity. Both opioid and dopamine signaling are involved in ethanol drinking to intoxication. Different physiological pathways mediate high ethanol drinking as compared to water or sugar water drinking in DID. DID may be a useful screening tool to find new alcoholism medications and to discover genetic and neurobiological mechanisms relevant to the human disorder.

In vitroandin vivomodels of acute alcohol exposure

“…In vivo the consumption of alcohol in one setting implies that the entire dose of alcohol is consumed at once, while a 'binge' is defined by NIAAA as an excessive pattern of alcohol drinking that produces BAL greater than 0.08% within a 2-h period and may, or may not, be associated with dependence [11,12,17,18] . Thus any model using consumption of biologically active amounts of alcohol within 2 h is considered an acceptable model of AAA [81,[107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] . (2) Establish an exposure to an accurate concentration of ethanol.…”

“…For in vitro studies the 10-100 mmol/L ethanol range is considered physiological, with 25 mmol/L ethanol being close to 0.08% BAL achieved in vivo after 4-5 drink equivalents [7,11,12,[98][99][100][101][102][103][104][105][106] . For the in vivo studies an 0.08% BAL or above this level yields signs of intoxication and it is employed in the majority of biomedical studies [107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] . (3) Recruit individuals who are currently not and never have been alcohol abusers for in vivo studies and employ alcohol-naïve primary cells or cell lines for in vitro studies.…”

“…Among non-human vertebrates commonly involved in alcohol research are primates [90,91,148] , pigs [104,120] , dogs [114,121] , mice [70,72,74,86,89,96,109,118,119,141] , rats [88,94,108,149,150] and rabbits [132] . The rodent AAA models (mice and rats) are used most frequently due to their relatively well-defined genetic background and the availability of diverse genetic traits, including those coding for high or low alcohol consumption [88,89,96,109] .…”

“…The rodent AAA models (mice and rats) are used most frequently due to their relatively well-defined genetic background and the availability of diverse genetic traits, including those coding for high or low alcohol consumption [88,89,96,109] . Most non-human AAA models currently in use [93,95] examine relative oral self-administration from a bottle containing alcohol versus one [86,94,108] or multiple bottles [119] containing water (preference drinking) or administration of alcohol against the will, either by physiological (by mouth using gavage)…”

Neurogenetic studies of alcohol addiction

“…However, the DID phenotype is proving to be a useful way to explore mechanisms underlying binge-like drinking. DID was shown to be reduced by intraperitoneal naltrexone doses that did not affect water or sugar-water intake (Kamdar et al 2007). Another group has shown that the GABA B agonist baclofen reduced ethanol DID without affecting water drinking, while two GABA A agonists, THIP and muscimol, reduced drinking nonspecifically (Moore et al 2007).…”