CHANGES INDUCED BY SODIUM CROMOGLYCATE IN BRAIN CATECHOLAMINE TURNOVER IN MORPHINE-DEPENDENT AND ABSTINENT MICE

The effects of sodium cromoglycate (CRO) were studied in relation to t he metabolism of brain catecholamines: dopamine (DA) and noradrenaline (NA), and their metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), h omovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylethyleneglycol (MH PG). CRO was injected SC in control mice, morphine-tolerant mice (tole rance was induced by SC implantation of a 75 mg morphine pellet; CRO w as administered on day 4 of addiction) and 30 min before abstinence (w ithdrawal was induced by SC injection of naloxone (1 mg/kg) on day 4 o f addiction). Brain catecholamines and their metabolites were measured using high performance liquid chromatography coupled with electrochem ical detection (HPLC-ECD), for DA, NA, DOPAC and HVA, and coupled with fluorescence detection for MHPG. The ratios of DOPAC + HVA/DA and MHP G/NA were kept as an index of DA and NA turnovers, respectively. CRO a dministered 30 min before naloxone-precipitated withdrawal diminished significantly NA levels in frontal cortex. CRO increased DA turnover i n striatum and frontal cortex in naive animals and significantly dimin ished DA levels in frontal cortex and DOPAC levels in frontal cortex a nd midbrain in morphine-dependent mice. These findings are discussed i n relation to the protective effects of CRO on opiate withdrawal and t he effects of CRO on locomotor activity.