Jaworska-Feil L, Budziszewska B, Lasoń W
Department of Endocrinology, Polish Academy of Sciences, Kraków, Poland.
Neuropeptides. 1997 Jun;31(3):253-8. doi: 10.1016/s0143-4179(97)90056-1.
The effects of single and repeated administration of cocaine on the thyrotropin-releasing hormone (TRH) level and receptors in discrete rat brain structures were evaluated. Male Wistar rats received saline or cocaine (15 mg/kg i.p., once an hour within 3 h, for 8 days). The animals were killed by decapitation at 45 min and 72 h (chronic group only) after the last injection. A radioimmunoassay (RIA) study showed that a single dose of cocaine increased the TRH level in the striatum by 68%, but had no significant effect on the peptide content in the nucleus accumbens, hippocampus, amygdala, septum, hypothalamus, frontal and prefrontal cortex at 45 min after the drug injection. Repeated administration of cocaine increased the TRH level in the striatum by 89% at 45 min, and in the hippocampus by 26% at 72 h after the last dose. No changes in the TRH level were found in other brain structures. In vitro cocaine (10(-6)-10(-4) M) inhibited the K(+)-stimulated release in a concentration-dependent manner, but had no effect on the basal release of TRH from the striatum and nucleus accumbens of naive rats. Acute cocaine decreased the Bmax of TRH receptors in the striatum, but had no effect on the density and affinity of TRH receptors in other brain regions. Repeated administration of cocaine evoked a long-lasting decrease in the Bmax of TRH receptors in the striatum (by c. 30%), whereas an increase in that parameter was observed in the frontal cortex. The Bmax and affinity of TRH receptors following repeated cocaine remained unchanged in the nucleus accumbens. The results obtained indicate that cocaine affects the TRH system mainly in the striatum, and to a lesser extent in the nucleus accumbens, cortex and hippocampus. Furthermore, the above changes do not resemble those induced by amphetamine, which points to certain differences in adaptation of the TRH neuronal system to these psychostimulants. On the other hand, the increase in the hippocampal TRH level during both chronic cocaine and morphine withdrawal is a common feature of the mechanism of dependence on these drugs.
评估了单次和重复给予可卡因对大鼠离散脑区促甲状腺激素释放激素（TRH）水平及受体的影响。雄性Wistar大鼠接受生理盐水或可卡因（15毫克/千克腹腔注射，3小时内每小时一次，共8天）。在末次注射后45分钟和72小时（仅慢性组）将动物断头处死。放射免疫分析（RIA）研究表明，单次给予可卡因使纹状体中TRH水平升高68%，但在药物注射后45分钟时，对伏隔核、海马、杏仁核、隔区、下丘脑、额叶和前额叶皮质中的肽含量无显著影响。重复给予可卡因在末次给药后45分钟时使纹状体中TRH水平升高89%，在72小时时使海马中TRH水平升高26%。在其他脑区未发现TRH水平有变化。体外实验中，可卡因（10⁻⁶ - 10⁻⁴ 摩尔/升）以浓度依赖方式抑制K⁺刺激的释放，但对未处理大鼠纹状体和伏隔核中TRH的基础释放无影响。急性给予可卡因降低了纹状体中TRH受体的最大结合容量（Bmax），但对其他脑区TRH受体的密度和亲和力无影响。重复给予可卡因导致纹状体中TRH受体的Bmax长期降低（约30%），而在额叶皮质中该参数则升高。重复给予可卡因后，伏隔核中TRH受体的Bmax和亲和力保持不变。所得结果表明，可卡因主要影响纹状体中的TRH系统，对伏隔核、皮质和海马的影响较小。此外，上述变化与苯丙胺诱导的变化不同，这表明TRH神经元系统对这些精神兴奋剂的适应性存在某些差异。另一方面，慢性可卡因和吗啡戒断期间海马中TRH水平升高是对这些药物产生依赖机制的一个共同特征。
