EFFECTS OF TREPELENNAMINE ON BRAIN MONOAMINE TURNOVER IN MORPHINE-DEPENDENT AND ABSTINENT MICE

Previous studies have reported that the histamine H-1 receptor blocker tripelennamine potentiates morphine withdrawal. In this paper, the in vivo effects produced by tripelennamine on the turnover of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in the whole brain, exclu ding the cerebellum, were studied in control, morphine-dependent (by S C implantation of a 75 mg morphine pellet) and morphine-dependent male CD1 mice just before naloxone-precipitated withdrawal. Tripelennamine (1-10 mg/kg) was administered SC 45 min before the animals were kille d. Serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA), dopamine, 3,4-di hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and noradren aline were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) and 3-methoxy-4-hydroxypheny lethyleneglycol (MHPG) was measured by HPLC coupled with fluorimetric detection. Ratios 5-HIAA/5-HT, DOPAC+HVA/DA and MHPG/NA were taken as an index of serotonin, dopamine and noradrenaline turnovers, respectiv ely. Tripelennamine (1 and 10 mg/kg) significantly reduced serotonin t urnover in control and morphine-dependent mice, and potentiated the se rotonin turnover reduction when it was administered 30 min before nalo xone injection. The dopamine turnover was diminished by tripelennamine (1 and 10 mg/kg) in the morphine-dependent group. Tripelennamine (10 mg/kg) reduced noradrenaline turnover during abstinence. These results suggest that the potentiation of opiate abstinence by tripelennamine could be related to its antiserotonergic profile.