Packard M G, Vecchioli S F, Schroeder J P, Gasbarri A
Department of Psychology, Yale University, New Haven, Connecticut 06520-8025, USA.
Learn Mem. 2001 Mar-Apr;8(2):96-103. doi: 10.1101/lm.37401.
The effect of post-training intradorsal striatal infusion of metabotropic glutamate receptor (mGluR) drugs on memory consolidation processes in an inhibitory avoidance (IA) task and visible/hidden platform water maze tasks was examined. In the IA task, adult male Long-Evans rats received post-training intracaudate infusions of the broad spectrum mGluR antagonist alpha-methyl-4-carboxyphenylglycine (MCPG; 1.0, 2.0 mM/0.5 microL), the group I/II mGluR agonist 1-aminocyclopentane-1,3-carboxylic acid (ACPD; 0.5 or 1.0 microM/0.5 microL), or saline immediately following footshock training, and retention was tested 24 h later. In the visible- and hidden-platform water maze tasks, rats received post-training intracaudate infusions of ACPD (1.0 microM), MCPG (2.0 mM), or saline immediately following an eight-trial training session, followed by a retention test 24 h later. In the IA task, post-training infusion of ACPD (0.5 and 1.0 microM) or MCPG (1.0 and 2.0 mM) impaired retention. In the IA and visible-platform water maze tasks, post-training infusion of ACPD (1.0 microM), or MCPG (2.0 mM) impaired retention. In contrast, neither drug affected retention when administered post-training in the hidden-platform task, consistent with the hypothesized role of the dorsal striatum in stimulus-response habit formation. When intradorsal striatal injections were delayed 2 h post-training in the visible-platform water maze task, neither drug affected retention, indicating a time-dependent effect of the immediate post-training injections on memory consolidation. It is hypothesized that MCPG impaired memory via a blockade of postsynaptic dorsal striatal mGluR's, while the impairing effect of ACPD may have been caused by an influence of this agonist on presynaptic "autoreceptor" striatal mGluR populations.
研究了训练后向背侧纹状体内注射代谢型谷氨酸受体(mGluR)药物对抑制性回避(IA)任务以及可见/隐藏平台水迷宫任务中记忆巩固过程的影响。在IA任务中,成年雄性Long-Evans大鼠在足部电击训练后立即接受尾状核内注射广谱mGluR拮抗剂α-甲基-4-羧基苯甘氨酸(MCPG;1.0、2.0 mM/0.5 μL)、I/II组mGluR激动剂1-氨基环戊烷-1,3-羧酸(ACPD;0.5或1.0 μM/0.5 μL)或生理盐水,并在24小时后测试记忆保持情况。在可见平台和隐藏平台水迷宫任务中,大鼠在八次训练后立即接受尾状核内注射ACPD(1.0 μM)、MCPG(2.0 mM)或生理盐水,随后在24小时后进行记忆保持测试。在IA任务中,训练后注射ACPD(0.5和1.0 μM)或MCPG(1.0和2.0 mM)会损害记忆保持。在IA和可见平台水迷宫任务中,训练后注射ACPD(1.0 μM)或MCPG(2.0 mM)会损害记忆保持。相比之下,在隐藏平台任务中训练后给药,两种药物均不影响记忆保持,这与背侧纹状体在刺激-反应习惯形成中的假设作用一致。在可见平台水迷宫任务中,当训练后2小时延迟进行背侧纹状体内注射时,两种药物均不影响记忆保持,表明训练后立即注射对记忆巩固具有时间依赖性效应。据推测,MCPG通过阻断突触后背侧纹状体mGluR来损害记忆,而ACPD的损害作用可能是由于该激动剂对突触前“自身受体”纹状体mGluR群体的影响所致。