Barium potentiates the conditioned aversion to, but not the somatic signs of, morphine withdrawal in mice

The effect of barium, a putative blocker of G-protein-activated inwardly rectifying potassium (GIRK) channels, on naltrexone-precipitated withdrawal signs in morphine-dependent mice was investigated. Mice were chronically treated with morphine (8-45 mg/kg) for 6 days. The morphine-dependent mice were then given naltrexone (1 and 3 mg/kg), after which they showed several somatic signs of withdrawal, as well as conditioned aversion, increased cortical noradrenaline turnover, and decreased dopamine turnover in the limbic forebrain. Pretreatment with barium (1.25 and 2.5 nmol) significantly potentiated the naltrexone-precipitated conditioned aversion and augmented the decrease in dopamine turnover in the limbic forebrain. However, barium pretreatment did not affect the naltrexone-precipitated somatic signs of withdrawal and increased cortical noradrenaline turnover. These findings suggest that modification of GIRK channels may be involved in the expression of aversion to morphine withdrawal mediated through the dopaminergic system but it is not involved in the somatic signs of morphine withdrawal mediated through the noradrenergic system.