Departament de Farmacia i Tecnología Farmacèutica, Universitat de València, Burjassot, Spain.
Psychopharmacology (Berl). 2010 Mar;209(1):1-11. doi: 10.1007/s00213-009-1751-9.
Microinjections of ethanol and acetaldehyde into ventral tegmental area (VTA) produce locomotor activation in rats through mechanisms dependent on the mu-opioid receptors. However, it is not clear how these drugs can interact with these receptors. It has been hypothesized that salsolinol could be the responsible for this interaction.
The aim of the study was to investigate the ability of salsolinol to induce both motor activation and motor sensitization in rats after repeated intra-VTA administration.
Rats received one microinjection into the posterior VTA of artificial cerebrospinal fluid (aCSF; 200 nL), salsolinol (0.3-3,000.0 pmol/200 nL), or salsolinol (30.0 pmol/200 nL) with either naltrexone (13.2 nmol/200 nL) or with the antagonist of the mu-opioid receptors, beta-funaltrexamine (beta-FNA; 2.5 nmol/300 nL). In the sensitization experiments, four microinjections of salsolinol (30.0 pmol/200 nL) or aCSF (200 nL) were performed over a 2-week period. This period was followed by a single challenge session, in which 0.3 pmol of salsolinol was microinjected to rats. Spontaneous activity was always monitored postinjection.
Intra-VTA salsolinol administration induces an increase of the spontaneous motor activity of the rats with the maximal effect at the dose of 30.0 pmol/200 nL. Salsolinol effects were blocked by the treatment with naltrexone or beta-FNA. Moreover, repeated injections of salsolinol produced locomotor sensitization.
Salsolinol induces locomotor activity and motor sensitization after intra-VTA administration. Moreover, the implication of the mu-opioid receptors was shown since the treatment with naltrexone or beta-FNA was able to suppress the salsolinol effects.
向腹侧被盖区(VTA)内微注射乙醇和乙醛会通过依赖μ-阿片受体的机制在大鼠中产生运动激活。然而,目前尚不清楚这些药物如何与这些受体相互作用。有人假设萨索林醇可能是导致这种相互作用的原因。
本研究的目的是研究萨索林醇在重复 VTA 内给药后诱导大鼠产生运动激活和运动敏化的能力。
大鼠接受了一次向 VTA 后区微量注射人工脑脊液(aCSF;200 nL)、萨索林醇(0.3-3000.0 pmol/200 nL)或萨索林醇(30.0 pmol/200 nL),同时给予纳曲酮(13.2 nmol/200 nL)或μ-阿片受体拮抗剂β-正丁啡烷(β-FNA;2.5 nmol/300 nL)。在敏化实验中,在 2 周的时间内进行了四次萨索林醇(30.0 pmol/200 nL)或 aCSF(200 nL)的微量注射。这段时间之后,对大鼠进行了单次挑战,其中微注射 0.3 pmol 的萨索林醇。注射后始终监测自发活动。
VTA 内萨索林醇给药导致大鼠的自发运动活动增加,最大效应在 30.0 pmol/200 nL 的剂量下。纳曲酮或β-FNA 的处理阻断了萨索林醇的作用。此外,重复注射萨索林醇可引起运动敏化。
VTA 内给药后,萨索林醇可引起运动活动和运动敏化。此外,μ-阿片受体的参与得到了证明,因为纳曲酮或β-FNA 的处理能够抑制萨索林醇的作用。