Exposure to high pressure may produce the 5-HT behavioral syndrome in rats.
In addition to the motor events associated with high pressure neurologic syndrome (HPNS), we have observed behavioral changes that resemble the 5-hydroxytryptamine (5-HT) syndrome in free-moving rats exposed to pressures up to 70 ATA. These include a flat body posture, head weaving, reciprocal forepaw treading, and hyperlocomotion. Such changes occur when brain 5-HT levels are raised or when 5-HT receptors are activated. We have therefore studied the behavior of rats at pressure treated either with saline or with one of the following drugs: p-chlorophenylalanine (pCPA) which depletes brain 5-HT by 85-90%, Wy 27587 which inhibits 5-HT reuptake, 5-hydroxytryptophan (5-HTP) and carbidopa which increase brain 5-HT synthesis, and quipazine which is a 5-HT receptor-agonist. After treatment, rats were individually exposed to pressure, and behavioral scores were made for 5 min every 10 ATA up to 70 ATA by an unbiased observer who was not aware of the treatment given. Analysis of all control rats indicated that only a flat body posture, forepaw treading, and hyperlocomotion were positively correlated with pressure, and these events were used in all subsequent analysis. Rats treated with pCPA with whole brain 5-HT levels reduced by 90% had scores significantly less than controls. Rats treated with Wy 27587 showed significantly increased scores. Rats treated with 5-HTP and quipazine failed to show a significant increase in scores. These results suggest that a modified form of the 5-HT syndrome occurs when rats are exposed to increased pressure, and the behavioral events seen are consistent with some activation of the 5-HT1A receptor subtype.
Division of Anaesthesia, Clinical Research Centre, Harrow, Middlesex.
B
B
Wardley-Smith
S
S
Hudson
C J
CJ
Doré
A
A
Charlett
A
A
Fletcher
N T
NT
Brammer
M C
MC
Minchin
K T
KT
Wann
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001274:Atmospheric Pressure; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002230:Carbidopa / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000209:etiology*; D010134:Fenclonine / Q000494:pharmacology; D006610:High Pressure Neurological Syndrome / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C058897:WY 27587; D009536:Niacinamide; D012701:Serotonin; D011814:Quipazine; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002230:Carbidopa; D010134:Fenclonine