Gárate-Pérez Macarena Francisca, Cáceres-Vergara Daniela, Tobar Francisca, Bahamondes Carolina, Bahamonde Tamara, Sanhueza Claudia, Guzmán Fanny, Sotomayor-Zárate Ramón, Renard Georgina M
Universidad de Santiago de Chile (USACH), Facultad de Ciencias Médicas, Escuela de Medicina, Centro de Investigación Biomédica y Aplicada (CIBAP), Santiago, Chile.
Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
Front Pharmacol. 2024 Jul 29;15:1411927. doi: 10.3389/fphar.2024.1411927. eCollection 2024.
The chronic use of psychostimulants increases the risk of addiction and, there is no specific pharmacologic treatment for psychostimulant addiction. The vasopressin (AVP) system is a possible pharmacological target in drug addiction. Previous results obtained in our laboratory showed that amphetamine (AMPH) treatment decreases lateral septum (LS) AVP levels in male rats, and AVP microinjection in LS decreases addictive-like behavior. The aim of the present work was to investigate the effect of AMPH treatment on LS AVP levels and the effect of LS AVP administration on the expression of AMPH-conditioned place preference (CPP) in female rats. The secondary objectives were to study the effect of LS AVP administration on LS GABA and glutamate release in male and female rats and on nucleus accumbens (NAc) dopamine (DA) release in female rats. Female rats were conditioned with AMPH (1.5 mg/kg i.p.) or saline for 4 days. Conditioning with AMPH did not change LS AVP content in females. However, AVP microinjection into the LS decreased the expression of conditioned place preference (CPP) to AMPH. Glutamate and GABA extracellular levels in the LS induced by AVP were studied in males and females. NAc GABA and DA extracellular levels induced by LS AVP microinjection in female rats were measured by microdialysis. In males, AVP perfusion produced a significant increase in LS GABA extracellular levels; however, a decrease in GABA extracellular levels was observed in females. Both in males and females, LS AVP perfusion did not produce changes in LS glutamate extracellular levels. Microinjection of AVP into the LS did not change GABA or DA extracellular levels in the NAc of females. Therefore, AVP administration into the LS produces different LS-NAc neurochemical responses in females than males but decreases CPP to AMPH in both sexes. The behavioral response in males is due to a decrease in NAc DA levels, but in females, it could be due to a preventive increase in NAc DA levels. It is reasonable to postulate that, in females, the decrease in conditioning produced by AVP microinjection is influenced by other factors inherent to sex, and an effect on anxiety cannot be discarded.
长期使用精神兴奋剂会增加成瘾风险，并且对于精神兴奋剂成瘾没有特定的药物治疗方法。血管加压素（AVP）系统可能是药物成瘾的一个药理学靶点。我们实验室之前获得的结果表明，给予雄性大鼠苯丙胺（AMPH）会降低其外侧隔核（LS）中的AVP水平，而向LS中微量注射AVP会减少成瘾样行为。本研究的目的是探究给予AMPH对雌性大鼠LS中AVP水平的影响，以及向LS中给予AVP对雌性大鼠AMPH条件性位置偏爱（CPP）表达的影响。次要目的是研究向LS中给予AVP对雄性和雌性大鼠LS中γ-氨基丁酸（GABA）和谷氨酸释放的影响，以及对雌性大鼠伏隔核（NAc）中多巴胺（DA）释放的影响。雌性大鼠用AMPH（1.5毫克/千克腹腔注射）或生理盐水处理4天。用AMPH处理并未改变雌性大鼠LS中的AVP含量。然而，向LS中微量注射AVP会降低对AMPH的条件性位置偏爱（CPP）的表达。研究了雄性和雌性大鼠中由AVP诱导的LS中的谷氨酸和GABA细胞外水平。通过微透析测量雌性大鼠中向LS微量注射AVP所诱导的NAc中GABA和DA的细胞外水平。在雄性大鼠中，灌注AVP会使LS中GABA的细胞外水平显著升高；然而，在雌性大鼠中观察到GABA的细胞外水平降低。在雄性和雌性大鼠中，灌注LS AVP均未使LS中谷氨酸的细胞外水平发生变化。向雌性大鼠的LS中微量注射AVP并未改变NAc中GABA或DA的细胞外水平。因此，向LS中给予AVP在雌性大鼠中产生的LS-NAc神经化学反应与雄性大鼠不同，但在两性中均会降低对AMPH的CPP。雄性大鼠的行为反应是由于NAc中DA水平降低，但在雌性大鼠中，可能是由于NAc中DA水平预防性升高。可以合理推测，在雌性大鼠中，AVP微量注射所产生的条件化降低受性别固有其他因素的影响，并且不能排除对焦虑的影响。
