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Aim:The conditioned place preference(CPP)paradigm was used to investigatethe effects of endogenous histamine on the processes leading to morphine-induced reward-seeking behavior in Sprague-Dawley rats.Methods:The modelof CPP was used to assess the rewarding effect of morphine.The levels of histamine,glutamate,γ-aminobutyric acid(GABA),dopamine(DA)and 3,4-dihydroxyphenyl-acetic acid(DOPAC)in rat brains were measured with high-performance liquidchromatography.Immunohistochemistry technique was used to observe themorphological changes of neurons.Results:Intraperitoneal injection of mor-phine(2,5 or 10 mg/kg)induced the development of CPP in a dose-dependentmanner.In addition,morphine administrations(10 mg/kg)decreased the hista-mine content and reduced the number and size of histaminergic neurons in thetuberomammillary nucleus(TM),as well as markedly increasing the DOPAC/DAratios in the ventral tegmental area(VTA)and nucleus accumbens(NAc).Intra-peritoneal injection of histidine(50,100 or 200 mg/kg)dose-dependently inhibitedthe development of morphine-induced CPP.Bilateral lesions of the TM,whichdecreased the histamine levels in the VTA and NAc,potentiated the developmentof CPP induced by morphine(1 mg/kg,a dose that produced no appreciable effectwhen given alone)and increased the DOPAC/DA ratios in the VTA and NAc,butdid not change the glutamate or GABA levels in these nuclei.Histidine reversedthe effects of the TM lesions.Conclusion:These results indicate that endog-enous histamine plays a role in inhibiting the development of morphine-inducedreward-seeking behavior,and the inhibition may involve the modulation of dopa-minergic activity.
Aim: The conditioned place preference (CPP) paradigm was used to investigate the effects of endogenous histamine on the processes leading to morphine-induced reward-seeking behavior in Sprague-Dawley rats. Methods: The model of CPP was used to assess the rewarding effect of morphine The levels of histamine, glutamate, γ-aminobutyric acid (GABA), dopamine (DA) and 3,4-dihydroxyphenyl-acetic acid (DOPAC) in rat brains were measured with high-performance liquid chromatography. Immunohistochemistry technique was used to observe themorphological changes of neurons. Results: Intraperitoneal injection of mor-phine (2,5 or 10 mg / kg) induced the development of CPP in a dose- dependent manner. In addition, morphine administrations (10 mg / kg) decreased the hista-mine content and reduced the number and size of histaminergic neurons in the tuberomammillary nucleus (TM), as well as markedly increasing the DOPAC / DAratios in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Intra-peritoneal injection of histidine r 200 mg / kg) dose-dependently inhibited the development of morphine-induced CPP.Bilateral lesions of the TM, which created the histamine levels in the VTA and NAc, potentiated the development of CPP induced by morphine (1 mg / kg, a dose that produced no appreciable effectwhen given alone) and increased the DOPAC / DA ratios in the VTA and NAc, but do not change the glutamate or GABA levels in these nuclei. Histidine reversed the effects of the TM lesions. Confc: These results indicate that endog-enous histamine plays a role in inhibiting the development of morphine-induced reward-seeking behavior, and the inhibition may involve the modulation of dopa-minergic activity.