Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine.
Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine.
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发表时间：
1993-10
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通讯作者：
P. Kalivas;J. E. Alesdatter
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作者：
P. Kalivas;J. E. Alesdatter
全身给予N-甲基-D-天冬氨酸（NMDA）拮抗剂可防止对苯丙胺类精神兴奋剂的行为敏感化。预处理与非竞争性NMDA拮抗剂，MK-801，导致可卡因的行为敏化的剂量依赖性封锁。然而，用最高剂量的MK-801（0.25 mg/kg i. p.）单独抑制24小时后对随后的可卡因攻击的行为反应。已知行为敏感化的诱导至少部分是由精神兴奋剂在腹侧被盖区（VTA）的作用引起的。为了确定NMDA拮抗剂对可卡因行为敏感化的剂量依赖性抑制是否由VTA中的受体阻断引起，在全身给予可卡因（30 mg/kg i. p.）之前，在VTA中用MK-801或竞争性NMDA拮抗剂3-（2-羧基哌嗪-4-基）丙基-1-膦酸预处理大鼠。2 - 3天后，大鼠单独用可卡因（15 mg/kg i. p.）激发。用NMDA拮抗剂预处理VTA可防止行为敏感化的表现。用MK-801进行颅内预处理也被用于参与精神兴奋剂诱导的致敏的丘脑核和杏仁核。然而MK-801在丘脑核中没有作用，当微量注射到腹侧杏仁核时，它阻止了对可卡因挑战的行为敏感化的表现。MK-801在腹侧被盖区的最小有效剂量为0.01 nmol，而在杏仁核中的最小有效剂量为1.0 nmol。这些数据表明，在VTA和杏仁核的NMDA受体的刺激是必要的可卡因的行为敏化的发展。
Systemic administration of N-methyl-D-aspartate (NMDA) antagonists prevents the development of behavioral sensitization to amphetamine-like psychostimulants. Pretreatment with the noncompetitive NMDA antagonist, MK-801, resulted in a dose-dependent blockade of behavioral sensitization to cocaine. However, pretreatment with the highest dose of MK-801 (0.25 mg/kg i.p.) alone inhibited the behavioral response to a subsequent cocaine challenge 24 hr later. The induction of behavioral sensitization is known to result, at least partly, from an action by psychostimulants in the ventral tegmental area (VTA). To determine whether the dose-dependent inhibition of behavioral sensitization to cocaine by NMDA antagonists resulted from receptor blockade in the VTA, rats were pretreated in the VTA with the MK-801 or the competitive NMDA antagonist, 3-(2-carboxypiperazine-4-yl) propyl-1-phosphonic acid, before systemically administered cocaine (30 mg/kg i.p.). Two to 3 days later rats were challenged with cocaine alone (15 mg/kg i.p.). Pretreatment with either NMDA antagonist into the VTA prevented the manifestation of behavioral sensitization. Intracranial pretreatment with MK-801 was also made into the nucleus accumbens and amygdala which have been implicated in psychostimulant-induced sensitization. Whereas MK-801 was without effect in the nucleus accumbens, when microinjected into the ventral amygdala it prevented the manifestation of behavioral sensitization to a cocaine challenge. The blockade of sensitization by MK-801 in the VTA was produced with a minimum effective dose of 0.01 nmol, whereas the minimum effective dose in the amygdala was 1.0 nmol. These data demonstrate that stimulation of NMDA receptors in the VTA and amygdala is necessary in the development of behavioral sensitization to cocaine.