Carvalho Juliana Dias Melo, de Oliveira Amanda R, da Silva Regina Claudia Barbosa, Brandão Marcus L
Instituto de Neurociências & Comportamento-INeC, Campus USP, 14040-901, Ribeirão Preto, SP, Brazil.
Pharmacol Biochem Behav. 2009 Apr;92(2):351-6. doi: 10.1016/j.pbb.2009.01.001.
In recent years, studies in behavioral pharmacology have shown the involvement of dopaminergic mechanisms in avoidance behavior as assessed by the two-way active avoidance test (CAR). Changes in dopaminergic transmission also occur in response to particularly threatening challenges. However, studies on the effects of benzodiazepine (BZD) drugs in this test are still unclear. Given the interplay of dopamine and other neurotransmitters in the neurobiology of anxiety and schizophrenia the aim of this work was to evaluate the effects of systemic administration of midazolam, the dopaminergic agonist apomorphine, and the D2 receptor antagonist sulpiride using the CAR, a test that shows good sensitivity to typical neuroleptic drugs. Whereas midazolam did not alter the avoidance response, apomorphine increased and sulpiride reduced them in this test. Escape was not affected by any drug treatments. Heightened avoidance was not associated with the increased motor activity caused by apomorphine. In contrast with the benzodiazepine midazolam, activation of post-synaptic D2 receptors with apomorphine facilitates, whereas the D2 receptor antagonism with sulpiride inhibited the acquisition of the avoidance behavior. Together, these results bring additional evidence for a role of D2 mechanisms in the acquisition of the active avoidance.
近年来，行为药理学研究表明，通过双向主动回避试验（CAR）评估，多巴胺能机制参与了回避行为。多巴胺能传递的变化也会因特别具有威胁性的挑战而发生。然而，关于苯二氮䓬（BZD）类药物在该试验中的作用研究仍不明确。鉴于多巴胺与其他神经递质在焦虑症和精神分裂症神经生物学中的相互作用，本研究的目的是使用对典型抗精神病药物具有良好敏感性的CAR试验，评估咪达唑仑全身给药、多巴胺能激动剂阿扑吗啡和D2受体拮抗剂舒必利的作用。在该试验中，咪达唑仑未改变回避反应，阿扑吗啡增强了回避反应，而舒必利则降低了回避反应。逃避行为不受任何药物治疗的影响。增强的回避反应与阿扑吗啡引起的运动活动增加无关。与苯二氮䓬类药物咪达唑仑相反，阿扑吗啡激活突触后D2受体会促进回避行为的习得，而舒必利拮抗D2受体则会抑制回避行为的习得。总之，这些结果为D2机制在主动回避行为习得中的作用提供了更多证据。
