Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug, of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors.
Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxy-tryptamine1A (5-HT1A) agonists 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) and 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT1A antagonistic activity. Direct microinjection of these 5-HT1A selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HT1A receptors.
Hirose
A
A
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Tsuji
R
R
Shimizu
H
H
Tatsuno
T
T
Tanaka
H
H
Kumasaka
Y
Y
Nakamura
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D054833:Isoindoles; D008845:Microinjections; D009281:Naphthalenes / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012154:Reticular Formation / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D009281:Naphthalenes; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C055267:tandospirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001285:Atropine; D010869:Pindolol