title: Effects of trepelennamine on brain monoamine turnover in morphine dependent and abstinent mice.
abstract: Previous studies have reported that the histamine H1 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, excluding the cerebellum, were studied in control, morphine-dependent (by SC 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 killed. Serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and noradrenaline were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) and 3-methoxy-4-hydroxyphenylethyleneglycol (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, respectively. Tripelennamine (1 and 10 mg/kg) significantly reduced serotonin turnover in control and morphine-dependent mice, and potentiated the serotonin turnover reduction when it was administered 30 min before naloxone 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.
authors.affiliation: Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
authors.forename: O
authors.initials: O
authors.lastname: San-Martin-Clark
authors.forename: B
authors.initials: B
authors.lastname: Cuellar
authors.forename: J C
authors.initials: JC
authors.lastname: Leza
authors.forename: I
authors.initials: I
authors.lastname: Lizasoain
authors.forename: P
authors.initials: P
authors.lastname: Lorenzo
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D019966:Substance-Related Disorders; D014309:Tripelennamine / Q000494:pharmacology*
chemical_list: D015306:Biogenic Monoamines; D014309:Tripelennamine; D009020:Morphine; D004298:Dopamine