Intracerebroventricular administration of endothelin-1 impairs the habituation of rats to a novel environment in conjunction with brain serotonergic activation.
The effects of i.c.v. administration of endothelin-1, at a low dose that does not produce abnormal behaviors such as barrel-rolling, on the emotional state of rats exposed to a novel environment were examined. Changes in the emotional state of rats with a novel environment were evaluated in terms of changes in exploratory activity in the hole-board apparatus, i.e., locomotor activity as well as the number and duration of rearing and head-dipping behaviors. Rats treated with i.c.v. saline showed marked exploratory behaviors immediately after exposure to the hole-board apparatus, but these exploratory behaviors decreased rapidly with time. On the other hand, the habituation of rats to a novel environment was prolonged by the i.c.v. administration of endothelin-1 (0.3 and 1 pmol). Furthermore, we also found that i.c.v. administration of endothelin-1 (1 pmol) significantly increased the serotonin (5-hydroxytryptamine) turnover in some brain regions, i.e., the cerebral cortex, hippocampus and midbrain, and the inhibition of brain 5-hydroxytryptamine synthesis by treatment with p-chlorophenylalanine (200 mg/kg/day, s.c.) for 2 days suppressed the behavioral effects of endothelin-1 (1 pmol, i.c.v.). In addition, i.c.v. administration of endothelin-1 (1 pmol) did not affect the spontaneous motor activity of rats. The present study demonstrated that i.c.v. administration of low doses of endothelin-1 impairs the habituation of rats to a novel environment in conjunction with brain 5-hydroxytryptaminergic activation. These results suggest that the central endothelin system may play a significant role in mediating emotionality.
Takeda
H
H
Department of Pharmacology and Intractable Diseases Research Center, Division of Drug Research and Development, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. ht0417@tokyo-med.ac.jp
Tsuji
M
M
Fujisawa
Y
Y
Yamada
T
T
Tsuji
K
K
Egashira
T
T
Matsumiya
T
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019332:Endothelin-1 / Q000008:administration & dosage*; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
D019332:Endothelin-1; D012701:Serotonin