JaLCDOI 10.18926/AMO/32836
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Author Gomita, Yutaka| Ichimaru, Yasuyuki| Moriyama, Minehiro| Araki, Hiroaki| Futagami, Koujiro|
Abstract <p>In considering the characteristics of the action of anxiolytic drugs and their mechanism in the brain, it may be necessary not only to study the behavioral pharmacology but also to perform brain site research. In the present study, the action of anxiolytic drugs was examined with respect to various behaviors that were induced by stimulating the brain areas related to emotions such as reward (pleasure) or aversion in rats. First, the low rate of response in lateral hypothalamic self-stimulation behavior was induced by schedules of low current brain stimulation, variable interval (VI) and differential reinforcement of low rate (DRL). Anxiolytic drugs such as benzodiazepines facilitated these low-rate responses. The drug susceptibility was highest in the low current stimulation, lower in the VI stimulation, and lowest in the DRL stimulation schedules. Furthermore, it was found by the auto-titration method in intracranial self-stimulation behavior that anxiolytic drugs decreased the threshold of stimulation reward. Second, it was recognized using the decremental lever pressing (DLP) paradigm that anxiolytic drugs increased the threshold of aversive stimulation of mesencephalic dorsal central gray (DCG), and this increasing effect of the drug was antagonized by GABA receptor blockers such as biccuculline. Finally, it was examined whether or not the conflict situation is established by combining brain stimulation reward and aversion, such as foot-shock or DCG stimulation. As a result, the conflict behavior was established by combining not only the brain stimulation reward and foot-shock aversion, but also the brain stimulation reward and DCG stimulation aversion. Further anxiolytic drugs exhibited anti-conflict action in both situations. The susceptibility of anxiolytic drugs was higher with respect to the conflict behavior induced by intracranial reward and aversion than to that induced by the conventional method based on milk reward and foot-shock aversion. These results suggest that behavioral methods using brain stimulation can examine the mechanisms of direct drug action at the brain stimulation site. Indeed, in the present brain stimulation behavioral study, anxiolytic drugs such as benzodiazepines increased the stimulation threshold in lateral hypothalamic self-stimulation and inhibited the DCG aversive stimulation, thus resulting in an anticonflict action of the drugs.</p>
Keywords anxiolytic drugs lateral hypothalamic self-stimulation escape behavior induced by mesencephalic dorsal central gray stimulation conflict behavior rats
Amo Type Review
Published Date 2003-06
Publication Title Acta Medica Okayama
Volume volume57
Issue issue3
Publisher Okayama University Medical School
Start Page 95
End Page 108
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 12908007
Web of Science KeyUT 000183816500001
JaLCDOI 10.18926/AMO/32017
FullText URL fulltext.pdf
Author Yamamoto, Takahiro| Araki, Hiroaki| Futagami, Koujiro| Kawasaki, Hiromu| Gomita, Yutaka|
Abstract <p>It is recognized that sustained ischemia-induced hyperactivity is related to abnormalities in dopamine function. However, it is unclear that dopaminergic neurotransmission triggers such ischemia-induced hyperactivity. Therefore, the relationship between dopaminergic neurotransmission and ischemia-induced hyperactivity was investigated in an animal model using Mongolian gerbils. When haloperidol 2 mg/kg was administered i.p. 30 min after ischemia, the ischemia-induced hyperactivity at 24 h after ischemia was blocked. General behavior was similar to that of sham-operated animals. Haloperidol at doses of 0.1 and 0.2 mg/kg had no effect on locomotor activity in sham-operated animals and decreased ischemia-induced hyperactivity when the drug was administered 24 h after ischemia; these doses did not have any effect on ischemia-induced hyperactivity when the drug was administered 30 min after ischemia. On the other hand, when the animal was confined to a small, restrictive cage for the 24 h period immediately following ischemic injury, locomotor activity at 24 h after ischemia increased. Such behavior also increased in animals when they were returned to their original more permissive cages immediately after ischemia. It is conceivable that the decrease in the level of activity was not related to ischemia-induced hyperactivity. These data suggested that the inhibition of ischemia-induced hyperactivity can be induced by complete blockage of dopaminergic receptors immediately after ischemia.</p>
Keywords ischemia hyperativity dopamine haloperidol Mongolian gerbils
Amo Type Article
Published Date 2001-11
Publication Title Acta Medica Okayama
Volume volume55
Issue issue5
Publisher Okayama University Medical School
Start Page 277
End Page 282
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11688950
Web of Science KeyUT 000171635400003
JaLCDOI 10.18926/AMO/32011
FullText URL fulltext.pdf
Author Futagami, Koujiro| Hirano, Naofumi| Iimori, Emiko| Motomura, Kenichi| Ide, Michiko| Kataoka, Yasuhumi| Araki, Hiroaki| Gomita, Yutaka| Oishi, Ryozo|
Abstract <p>Non-traumatic rhabdomyolysis associated with organophosphate intoxication has not been generally reported. We report here in a severe case of fenitrothion poisoning complicated by rhabdomyolysis. A 43-year-old woman ingested approximately 100 ml of fenitrothion emulsion (50%) in an attempt to commit suicide. On day 3 after admission, her creatine phosphokinase (CPK) peaked at 47,762 IU/L. She received supportive treatment included sodium bicarbonate and fluid resuscitation. However, muscarinic symptoms including excessive miosis and salivation developed on day 5 when her CPK levels decreased. The delay in cholinergic symptoms might have been due to the trihexyphenidyl she took with the antipsychotic drugs. Fortunately, the present patient recovered from the acute cholinergic crisis, and acute renal failure was prevented by early diagnosis. This is a case of organophosphate poisoning complicated by rhabdomyolysis in a psychiatric patient. The masking of acute cholinergic symptoms should be taken into consideration in such patients.</p>
Keywords fenitrothion organophosphate poisoning rhabdomyolysis psychiatric patient
Amo Type Article
Published Date 2001-04
Publication Title Acta Medica Okayama
Volume volume55
Issue issue2
Publisher Okayama University Medical School
Start Page 129
End Page 132
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 11332199
Web of Science KeyUT 000168195700009
JaLCDOI 10.18926/AMO/31615
FullText URL fulltext.pdf
Author Araki, Hiroaki| Kawasaki, Machiko| Matsuka, Naoyuki| Nakatsuma, Akira| Watanabe, Kazuhide| Futagami, Koujiro| Gomita, Yutaka|
Abstract <p>The effects of exposure to cigarette smoke on the pharmacokinetics and pharmacodynamics of zonisamide, an antiepileptic drug, were investigated in rats. Absorption of oral zonisamide was significantly inhibited by exposure to cigarette smoke. The Cmax, T1/2 and the area under the plasma concentration-time curve 0-24 values in the cigarette smoke exposure group were significantly lower than those in the control group. Although tonic extension (TE) induced by maximal electroshock was completely blocked by the administration of zonisamide in the control group, 50% of rats showed TE in the cigarette smoke exposure group. Exposure to cigarette smoke influences both the pharmacokinetics and antiepileptic effects of zonisamide. The effects of smoking on epileptic patients using zonisamide warrants further attention.</p>
Keywords cigarette smoking nicotine absorption convulsion zonisamide
Amo Type Article
Published Date 1999-08
Publication Title Acta Medica Okayama
Volume volume53
Issue issue4
Publisher Okayama University Medical School
Start Page 185
End Page 188
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 10488405
Web of Science KeyUT 000082334300004