Abstract herein anxiety related neurotransmitters (amino acids, monoamines, neuropeptides) studies and animal models of anxiety (elevated plus lost eg, dark box, the conflict model, etc.) studies were reviewed, and to perform anxiolytic Mechanism research provides a reference.
ã€Key words】 Anxiety ; Neurotransmitter ; Model , Animal
Commonly used animal models of anxiety are divided into two categories , one based on spontaneous reactions , such as exploratory tests ( shadow boxes, etc. ), which reflect anxiety states ( depressive anxiety ) caused by uncontrollable stress , while another type of model is based on conditioned reflexes. ( such as drinking water conflict experiments, etc. ) reflects the anxiety caused by controllable stress. This article will review the study of neurotransmitters and animal models related to anxiety.
1 amino acid
111 　 R2 aminobutyric acid (GABA) GABA is an inhibitory neurotransmitter widely distributed in the mammalian central nervous system. Among them, GABAA receptor plays an important role in the occurrence of anxiety. The current study found that GABAA receptors may play through six different binding sites , of which BDZ drugs such as BDZ receptor agonists have become classic anti-anxiety drugs , while barbiturates , indomethacins And so on. The classical animal models ( such as EPM, etc. ) widely used at present are based on the sensitivity of BDZ drugs , and thus provide a good platform for screening BDZ drugs. EPM the conflict based on the formation of new environment to explore the behavior of animals and the fear of hanging open arms, often times (OE) into the open arms and stay in the% open arm time (OT)% as a measure of anxiety, and The number of times the closed arm is entered (CE) is used for the detection of autonomous activity. Dalvi et al found that in the EPM of mice , diazepam significantly increased OE and OT, and the distribution of EPM time was significantly changed ( control group was closed arm > middle area > open arm , and after setting is closed arm > middle area = open arm ) , showing significant anti-anxiety effects , while stability also affects some risk-evaluating behaviors in EPM , such as reducing the number of uprights , erect time , and back-extension behavior
(flat2back approach behavior), grooming behavior, etc. Since flumazenil BDZ receptor antagonist can block the action of diazepam on inquiry upright behavior, suggesting different mechanisms affect the behavior of other upstanding mouse exploratory behavior in the EPM. EPM and similar animals explore the characteristics of the central region of the opening formed in a conflicted state test (OFT) and animal haptotactic, Choleris study showed stability and the like having a position-dependent role in OFT, settled in the haptotactic Areas ( such as the corner area ) can significantly reduce the behavior of stretched attend postures (SAP), reentry , buttress exploration , walking , sitting , grooming , and other behaviors in other areas. GABAA receptor antagonist printing anti- hexatoxin can be used in OFT
Dependent decrease the amount of activity (movement distance) of the central area of rats, the central area into the frequency and time at the central area, showed significant anxiety states, and the like but simultaneously Sienkiewicz receptor binding analysis revealed that these changes and acts GABAA Receptor expression is not directly related. The Vogel Conflict Model (VCT), based on conditioning , uses animal treadiness and fear of drinking water to create animal conflicts. In this model , stability can significantly increase the number of drip cycles (LN) during the penalty period , with a dose-dependent
Anti-collision effect.
Glutamic acid
In contrast to GABA, glutamate as a major excitatory neurotransmitter widely distributed in the whole brain, interact with the dopamine system, maintain brain excitatory and inhibitory balance of the state, causing arousal and anxiety. Glutamate receptors include NMDA , AMPA and kainate receptors , the latter two are called non2NMDA receptors , which are abundantly expressed in the DPAG region ( including amygdala , medial hypothalamus, etc. ), DPAG region and expression of aversive P defense behavior. And so on. Using the EPM model , it was found that microinjection of NMDA receptor antagonist AP7, CNQX (AMPAPkainite antagonist and GDEE ( non-selective glutamate antagonist )) in the DPAG region can increase OE % without affecting the number of times of entering the closed arm. , showing selective anxiolytic effects. But they
There are also subtle differences in the role , such as GDEE increases OT, while the same dose of CNQX does not affect OT . In addition , Matheu et al
Also found that DPAG play an important role in the area of anxiety because CNQX and GDEE outside the injection area DPAG had no effect.
2 monoamines - serotonin (52HT)
52HT is widely present in brain regions associated with anxiety , particularly the hypothalamic palpebral region and the amygdala. As a highly complex system , the 52HT receptor includes at least 7 families and 14 subtypes. Among them, 52HT1A receptors distributed in the substantia nigra, globus pallidus and striatum have attracted much attention . Studies have shown that the diversity of action of 52HT1A receptor agonists may depend on different sites of action , and their anxiolytic effects may act on spinal nucleus The pre-contact receptor , while acting on the postsynaptic receptor, produces an anxiogenic response. In addition , 52HT2c receptor , 52HT3 receptor , 52HTT (52HT transporter ) are involved in the occurrence of anxiety.
Using the EPM model, it was found that 52HT3A knockout mice had increased OE, OT and movement distance in the open arms , showing decreased anxiety , while 52HT6 mRNA antisense oligonucleotide AO decreased (OT)%, but did not affect the total of both arms. The number of entry and (OE)%, 52HTT (52HT transporter ) knockout mice reduced OT, showing an increase in anxiety. On the basis of the classic EPM , a series of improved models have been established , such as the elevated T- maze (ETM) and the elevated circular maze. ZanoveliJM found that elevated T maze (ETM), the periaqueductal gray backside nucleus (dPAG) administering 52HT region and 52HT2BP2C agonist MCPP rat avoidance latencies increase, contrary 52HT1A 82OH2DPAT receptor agonist action, 52HT2A receptor The agonist DOI had no effect , suggesting that the 52HT1A and 52HT2C receptors produced an opposite regulation of inhibitory avoidance. At the same time, Mcpp can also inhibit the one-way escape of rats . Because inhibition avoidance is related to GAD behavior , one-way escape is related to PD behavior , suggesting that the back side water conduit gray matter 52HT is also involved in PD and GAD -like reactions. Overhead circular maze , Toth M
It was also reported that the number of 52HT1A receptor knockout mice entering the open area and the time in the open area was significantly reduced , similar to the EPM results.
In the OFT, 52HT1A receptor knockout mice, 52HTT central region knockout mice In addition to reducing activity, haptotactic increased, and the display
EPM results in consistent anxiety behavior increased. In addition , OFT is also commonly used in animal autonomous activity research , and is complementary to other models to determine the specificity of anti-anxiety or anxiety-causing effects , such as 52HT3A gene knockout, 52HT6 mRNA antisense oligonucleotide AO does not affect mice in The total exercise or mean distance in the OFT , compared with the significant effect in the EPM , indicates that the reduction or increase in anxiety is not related to general inquiry and autonomous activities. Another classic anxiety model is based on the characteristics of rodent hilarity and good inquiry , and is a simple and easy method for screening. A trial showed that the controversial effect only 52HT3 receptor antagonists show anxiolytic effects in stabilizing the dark box, 52HT3A significant increase in gene knock out mice in addition to the time zone, the number of entries while exhibiting a high degree of open arm Correlation , while the time of 52HTT knockout mice decreased in the bright area
, showing an anxiety state. Social group test (SI) experiments produced changes in light intensity and familiarity with the active area . 52HT6 mRNA antisense oligonucleotide AO increased the active contact time (SI) in rats and showed an anxiolytic effect. In addition , in the novelty experiment , 52HT1A receptor knockout mice have less time to explore new things , and to explore activities and proximity. S. Zhao, etc.
It was also found that the number of burial times of 52HTT2P2 mice was reduced in the burial test , which further confirmed that 52HT1A receptor and 52HTT were involved in anxiety response.
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