Endogenous histamine inhibits the development of morphine-induced conditioned place preference

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.

The model of CPP was used to assess the rewarding effect of morphine. The levels of histamine, glutamate, gamma-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.

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 tubero-mammillary 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.

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.