Castilho V M, Macedo C E, Brandão M L
Laboratório de Psicobiologia, FFCLRP, Campus USP, Av. Bandeirantes 3900, 14040-901 Ribeirão Preto, SP, Brazil.
Psychopharmacology (Berl). 2002 Dec;165(1):77-85. doi: 10.1007/s00213-002-1246-4. Epub 2002 Oct 24.
The dorsal periaqueductal gray matter (dPAG) has been implicated in the modulation of defensive behavior. Electrical stimulation of this structure can be used as an unconditioned stimulus to produce a conditioned fear reaction expressed by freezing, antinociception, and autonomic responses.
This study investigated the influence of benzodiazepine, serotonergic, and opioid mechanisms on these conditioned responses.
Animals implanted with an electrode and a guide cannula into the dPAG were submitted to two conditioning sessions. Each session consisted of ten pairings of the light in a distinctive chamber (CS) with the electrical stimulation of this structure at the escape threshold. On the next day, each animal was exposed only to the CS (testing) and the duration of freezing, number of rearing and grooming episodes were recorded for 5 min. Before and after the testing session, animals were submitted to the tail-flick test. Fifteen minutes before the exposure to the CS, animals received injections into the dPAG of midazolam (a positive modulator of benzodiazepine sites), alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT; an agonist of 5-HT(2) receptors), naltrexone (an opioid antagonist), or vehicle.
Conditioning with dPAG electrical stimulation caused significant increases in the time of freezing and conditioned antinociception. Injections of midazolam into the dPAG significantly inhibited freezing behavior and antinociception due to conditioning. Injections of alpha-Me-5-HT inhibited the effects of conditioning on freezing without affecting conditioned antinociception. Injections of naltrexone (13 nmol/0.2 micro l) did not change any of the conditioned responses studied.
(1) Conditioned freezing and antinociception are modulated by benzodiazepine mechanisms into dPAG. (2) 5-HT(2) receptors seem to regulate conditioned freezing behavior. However, conditioned antinociception was not affected by 13 nmol naltrexone. (3) Opioid mechanisms do not seem to be involved in the conditioned responses using electrical stimulation of the dPAG as unconditioned stimulus. Further studies with other opioid and 5-HT(2) receptor antagonists are still needed to confirm the conclusions drawn from the present work.
中脑导水管周围灰质背侧（dPAG）与防御行为的调节有关。对该结构进行电刺激可作为一种非条件刺激，以产生由僵住、抗伤害感受和自主反应所表现出的条件性恐惧反应。
本研究调查了苯二氮䓬、血清素能和阿片类机制对这些条件反应的影响。
将电极和引导套管植入dPAG的动物接受两次条件训练。每次训练包括在一个独特的小室中，将灯光（条件刺激，CS）与该结构在逃避阈值下的电刺激进行十次配对。第二天，每只动物仅暴露于CS（测试），并记录5分钟内的僵住持续时间、站立和梳理次数。在测试前和测试后，动物接受甩尾试验。在暴露于CS前15分钟，动物接受向dPAG注射咪达唑仑（苯二氮䓬位点的正性调节剂）、α-甲基-5-羟色胺（α-Me-5-HT；5-HT(2)受体激动剂）、纳曲酮（阿片类拮抗剂）或赋形剂。
用dPAG电刺激进行条件训练导致僵住时间和条件性抗伤害感受显著增加。向dPAG注射咪达唑仑可显著抑制因条件训练引起的僵住行为和抗伤害感受。注射α-Me-5-HT可抑制条件训练对僵住的影响，而不影响条件性抗伤害感受。注射纳曲酮（13 nmol/0.2 μl）未改变所研究的任何条件反应。
（1）条件性僵住和抗伤害感受受dPAG中的苯二氮䓬机制调节。（2）5-HT(2)受体似乎调节条件性僵住行为。然而，13 nmol纳曲酮未影响条件性抗伤害感受。（3）阿片类机制似乎不参与以dPAG电刺激作为非条件刺激的条件反应。仍需用其他阿片类和5-HT(2)受体拮抗剂进行进一步研究，以证实从本研究得出的结论。
