THE BENZODIAZEPINE INVERSE AGONIST DMCM AS AN UNCONDITIONAL STIMULUS FOR FEAR-INDUCED ANALGESIA - IMPLICATIONS FOR THE ROLE OF GABA-A RECEPTORS IN FEAR-RELATED BEHAVIOR

被引:47
作者
FANSELOW, MS
KIM, JJ
机构
[1] University of California, Los Angeles
关键词
D O I
10.1037/0735-7044.106.2.336
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
When the benzodiazepine inverse agonist DMCM (6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methyl ester) occupies the benzodiazepine recognition site on the GABA(A) receptor complex, the inhibitory action of gamma-aminobutyric acid (GABA) is attenuated. DMCM acted as an unconditional stimulus for one response associated with fear or anxiety, analgesia, as indicated by a dose-dependent (0.25-1.0 mg/kg) suppression of rats' responses to a formalin injection. This was accompanied by other fearlike responses (defecation and urination). The opioid antagonist naltrexone (1.75-14 mg/kg) did not affect these behaviors. Environmental cues associated with DMCM provoked analgesia and defecation in the absence of the drug. The conditional analgesia was reversed by naltrexone (7 mg/kg). DMCM functions as an unconditional fear stimulus by eliciting fear-related behaviors and conditioning those responses to neutral stimuli. The neural circuitry underlying fear conditioning appears to involve tonically inhibitory GABAergic synapses.
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页码:336 / 344
页数:9
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