Endogenous histamine inhibits the development of morphine-induced conditioned place preference
Abstract
Aim: The conditioned place preference (CPP) paradigm was used to investigate
the effects of endogenous histamine on the processes leading to morphineinduced
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-dihydroxyphenylacetic
acid (DOPAC) in rat brains were measured with high-performance liquid
chromatography. Immunohistochemistry technique was used to observe the
morphological changes of neurons. Results: Intraperitoneal injection of morphine
(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 histamine
content and reduced the number and size of histaminergic neurons in the
tuberomammillary nucleus (TM), as well as markedly increasing the DOPAC/DA
ratios in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Intraperitoneal
injection of histidine (50, 100 or 200 mg/kg) dose-dependently inhibited
the development of morphine-induced CPP. Bilateral lesions of the TM, which
decreased 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 effect
when given alone) and increased the DOPAC/DA ratios in the VTA and NAc, but
did not change the glutamate or GABA levels in these nuclei. Histidine reversed
the effects of the TM lesions. Conclusion: These results indicate that endogenous
histamine plays a role in inhibiting the development of morphine-induced
reward-seeking behavior, and the inhibition may involve the modulation of dopaminergic
activity.
Keywords:
the effects of endogenous histamine on the processes leading to morphineinduced
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-dihydroxyphenylacetic
acid (DOPAC) in rat brains were measured with high-performance liquid
chromatography. Immunohistochemistry technique was used to observe the
morphological changes of neurons. Results: Intraperitoneal injection of morphine
(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 histamine
content and reduced the number and size of histaminergic neurons in the
tuberomammillary nucleus (TM), as well as markedly increasing the DOPAC/DA
ratios in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Intraperitoneal
injection of histidine (50, 100 or 200 mg/kg) dose-dependently inhibited
the development of morphine-induced CPP. Bilateral lesions of the TM, which
decreased 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 effect
when given alone) and increased the DOPAC/DA ratios in the VTA and NAc, but
did not change the glutamate or GABA levels in these nuclei. Histidine reversed
the effects of the TM lesions. Conclusion: These results indicate that endogenous
histamine plays a role in inhibiting the development of morphine-induced
reward-seeking behavior, and the inhibition may involve the modulation of dopaminergic
activity.