Jaffe A B, Sharpe L G, Jaffe J H
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Psychopharmacology (Berl). 1989;99(3):289-93. doi: 10.1007/BF00445545.
An ultrasonic nebulizer was used to create a drug vapor to develop an animal model for the self-administration of inhaled nonvolatile psychoactive drugs. An aerosol mist of a sufentanil citrate solution (10, 25, 50, or 75 micrograms/ml) was delivered to rats in response to lever presses on an FR 5 schedule of reinforcement. The speed of acquisition of the operant response and the selectivity of the drug effect were examined. Rats given access to sufentanil vapor (50 or 75 micrograms/ml) in 13-15 h overnight training sessions reached an average of one reinforcement per hour on an FR 5 schedule of reinforcement significantly sooner than did rats given access to water vapor. Responding maintained by sufentanil during 2-h daily testing sessions was dose dependent at 25, 50, and 75 micrograms/ml. Substituting water vapor for each of the four sufentanil concentrations significantly reduced responding within 5-20 sessions. Naloxone (1 mg/kg, IP) decreased responding for sufentanil to the level attained under water vapor. Presentation of drugs in aerosol form thus provides reasonable means of demonstrating in animals the reinforcing properties of non-volatile drugs by the pulmonary or intranasal route.
使用超声雾化器产生药物蒸汽,以建立吸入性非挥发性精神活性药物自我给药的动物模型。根据固定比率5强化程序,当大鼠按压杠杆时,将枸橼酸舒芬太尼溶液(10、25、50或75微克/毫升)的气溶胶雾输送给大鼠。研究了操作性反应的习得速度和药物效应的选择性。在13 - 15小时的夜间训练中,能够接触到舒芬太尼蒸汽(50或75微克/毫升)的大鼠,在固定比率5强化程序下,平均每小时获得一次强化的时间明显早于接触水蒸气的大鼠。在每天2小时的测试中,由25、50和75微克/毫升舒芬太尼维持的反应呈剂量依赖性。用四种舒芬太尼浓度中的每一种替代水蒸气,在5 - 20次实验中显著减少了反应。纳洛酮(1毫克/千克,腹腔注射)将对舒芬太尼的反应降低到水蒸气条件下达到的水平。因此,以气溶胶形式呈现药物为在动物中通过肺部或鼻内途径证明非挥发性药物的强化特性提供了合理的方法。