Biomaterial Database

[Effects of conditioned fear stress on monoaminergic systems in the rat brain]. 1993

T Inoue

Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.

The effects of conditioned fear stress (CFS), an animal model of anxiety, on brain dopamine (DA) and serotonin (5-HT) metabolism and behavior were investigated in rats. CFS (exposure to an environment paired previously with footshock) after single footshock stress increased plasma corticosterone levels and defecation, and induced freezing behavior. It also increased 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the medial prefrontal cortex (mPFC), paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamus, increased homovanillic acid (HVA) levels in the mPFC and amygdala, and increased 5-hydroxyindoleacetic acid (5-HIAA) level in the mPFC. Rats exposed to the stress for 10 days displayed enhanced freezing induced by CFS compared to rats given only one footshock session, according to the augmentation of fear. CFS after repeated footshock increased DOPAC levels in all seven brain regions and HVA levels in the mPFC, nucleus accumbens, amygdala and hippocampus. It also increased 5-HIAA levels in the mPFC and PVH. Thus, it was deduced that CFS after repeated footshock activated DA and 5-HT metabolism not only in the mPFC but also in other various brain regions, whereas increased metabolism of both DA and 5-HT was marked in the mPFC after CFS following a single footshock. In behavioral pharmacological experiments, the effects of various serotonergic agents and diazepam on CFS-induced freezing behavior were examined. The benzodiazepine diazepam (1mg/kg) and the selective 5-HT1A agonist ipsapirone (0.5-10mg/kg) significantly reduced freezing. The augmentation of 5-HT activity by the 5-HT precursor (L-5-HTP) and the selective 5-HT reuptake inhibitor (citalopram) also attenuated freezing. The 5-HT synthesis inhibitor PCPA failed to change freezing. In conclusion, these results suggest that the anxiolytic effect of ipsapirone results from the activation of postsynaptic 5-HT1A receptors and the facilitation of 5-HT neurotransmission decreases anxiety. This model may be useful for detecting the anxiolytic potential for drugs and examining the relationship of 5-HT to anxiety.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D003213	Conditioning, Psychological	Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response.	Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005239	Fear	The affective response to an actual current external danger which subsides with the elimination of the threatening condition.	Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D006719	Homovanillic Acid	A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid.	3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic
D006897	Hydroxyindoleacetic Acid		5-HIAA,5-Hydroxy-3-Indoleacetic Acid,5-Hydroxyindolamine Acetic Acid,5 Hydroxy 3 Indoleacetic Acid,5 Hydroxyindolamine Acetic Acid,Acetic Acid, 5-Hydroxyindolamine,Acid, 5-Hydroxy-3-Indoleacetic,Acid, 5-Hydroxyindolamine Acetic,Acid, Hydroxyindoleacetic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001007	Anxiety	Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.	Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D001522	Behavior, Animal	The observable response an animal makes to any situation.	Autotomy Animal,Animal Behavior,Animal Behaviors