Central and peripheral injection of quaternary antagonist, SR58002C, reduces drinking

Earlier research has demonstrated that opioid involvement in drinking is primarily mediated centrally [8,10]. Drinking is attenuated by the centrally and peripherally active opioid antagonists naloxone and naltrexone in doses as low as 1.0 mg/kg, but not by the quaternary forms of these antagonists [4]. Peripherally administered quaternary forms of these antagonists fail to suppress drinking in doses as high as 10 mg/kg. We generated dose-response curves for centrally and peripherally administered SR58002C, a "newer" quaternary opioid antagonist purported to have high peripheral selectivity, on drinking in 23.5 hr water deprived rats. SR58002C was administered both intracerebroventricularly (ICV, 0, 10, 40 and 80 micrograms/rat) and intraperitoneally (IP, 0, 10, 40 and 80 mg/kg). Doses of SR58002C above 10 mg/kg IP or 10 micrograms ICV significantly reduced drinking in comparison to controls. However, SR58002C appears to be less potent than quaternary naltrexone in suppressing drinking after ICV administration.