Compulsive drug-seeking motivation in rats provoked by escalating high-dose morphine pretreatment and the dopaminergic and nondopaminergic neuron activity in midbrain / 中华行为医学与脑科学杂志

ABSTRACT

Objective To probe the different expression of psychomotor in different model of pretreatment and the influence of pretreatment context on the expression of psychomotor.And to compare dopaminergic and non-dopaminergic neuron activity in midbrain after different pretreatment.Methods Rats were pretreated by escalated high-dose morphine( HD group) ,fixed low-dose morphine( LD group) and saline as control(S group).After withdrawal, rats were challenged by morphine in non-drug used environment.Locomotor behavior and stereotypy behavior were monitored as the index of compulsive drug-seeking motivation.By double labeling immunohistochemistry of tyrosine hydroxylase (TH) and Fos protein, the plasticity of neuronal activity in ventral tegmental area and substantia nigra of rats response to morphine challenge were disclose after pretreated with morphine or saline.Results After 10 mg/kg morphine challenge in non-drug used environment,the locomotor behavior and the stereotypy behavior of HD group were both significant higher than that of S group ( Locomotor behavior and Stereotypy behavior,HD group 26907 ± 2003 and 129.6 ± 6.5; S group 14962 ± 1888 and 89.9 ± 10.9, all P ＜ 0.01 ).The results of immunohistochemistry showed that Fos protein expressed in the SNr and in lateral SNr was significantly higher in the HD group compared to S groups ( Fos expression in SNr and lateral SNr,HD group 29.14 ±5.27 and 9.83 ± 2.84; S group 17.29 ± 1.51 and 2.06 ±0.45; all P＜0.05 ).Conclusion The sensitization behavior expression of the rat pretreated by escalated high-dose morphine is not modulated by drug using enviroment compared with fixed low-dose morphine pretreatment.The neuroplasticity of SNr,especially lateral SNr might be one of the mechanisms underlying the uncontroled sensitization behavior expression.