Birrell C E, Balfour D J
Department of Pharmacology and Neuroscience, University of Dundee Medical School, Ninewells Hospital, UK.
Psychopharmacology (Berl). 1998 Nov;140(2):142-9. doi: 10.1007/s002130050751.
Pretreatment with psychostimulant drugs causes sensitisation of their effects on locomotor activity and dopamine (DA) overflow in the nucleus accumbens (NAcc) and there is evidence for similarities in the mechanisms involved. This study used in vivo microdialysis in conscious freely moving rats to investigate the extent to which pretreatment with nicotine causes sensitisation to D-amphetamine. Pretreatment with nicotine (0.4 mg/kg s.c. daily for 5 days) caused sensitisation of the locomotor responses to D-amphetamine (0.1-0.5 mg/kg s.c.) but not cocaine (15 mg/kg i.p.). Nicotine pretreatment did not influence the increase in DA overflow into dialysis probes, located in the core of the NAcc, evoked by systemic injections of D-amphetamine or cocaine (15 mg/kg i.p.) but decreased the overflow evoked by the administration of D-amphetamine (1 x 10(-6) M) through the dialysis probe. The results provide further evidence for a dissociation between the expression of sensitised locomotor responses to psychostimulant drugs and sensitisation of their stimulatory effects on DA overflow in the core of the NAcc. The results suggest that the sensitisation of the effects of nicotine on DA overflow in this subdivision of the NAcc may be pharmacologically specific to nicotinic drugs.
使用精神兴奋药物进行预处理会使其对运动活动以及伏隔核(NAcc)中多巴胺(DA)溢出的影响产生敏化,并且有证据表明其中涉及的机制存在相似性。本研究采用清醒自由活动大鼠体内微透析技术,以探究尼古丁预处理对D-苯丙胺敏化的程度。尼古丁预处理(每天皮下注射0.4mg/kg,共5天)导致对D-苯丙胺(0.1 - 0.5mg/kg皮下注射)的运动反应敏化,但对可卡因(15mg/kg腹腔注射)则无此作用。尼古丁预处理并不影响全身注射D-苯丙胺或可卡因(15mg/kg腹腔注射)所引起的位于NAcc核心的透析探针中DA溢出的增加,但却降低了通过透析探针给予D-苯丙胺(1×10⁻⁶M)所引起的溢出。这些结果为精神兴奋药物敏化的运动反应表达与其对NAcc核心中DA溢出的刺激作用敏化之间的分离提供了进一步的证据。结果表明,尼古丁对NAcc这一细分区域中DA溢出影响的敏化在药理学上可能对烟碱类药物具有特异性。