Altered behavioral response to centrally acting drugs in mice lacking PACAP.
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Accession number;04A0001872
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| Title;Altered behavioral response to centrally acting drugs in mice lacking PACAP. |
| Author;
SHINTANI NORIHITO
(Osaka Univ., Graduate School of Pharmaceutical Sciences, JPN)
TANAKA KAZUHIRO
(Osaka Univ., Graduate School of Pharmaceutical Sciences, JPN)
HASHIMOTO HITOSHI
(Osaka Univ., Graduate School of Pharmaceutical Sciences, JPN)
BABA AKEMICHI
(Osaka Univ., Graduate School of Pharmaceutical Sciences, JPN)
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Journal Title;Folia Pharmacologica Japonica
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Journal Code:G0740A
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ISSN:0015-5691
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VOL.122;NO.;PAGE.1P-4P(2003)
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| Figure&Table&Reference;TBL.1, REF.17 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Mice lacking PACAP (PACAP-KO) exhibits altered psychomotor behaviors, including impaired habituation to a novel environment and perseverative jumping, with a slightly reduced levels of the serotonin metabolite, 5-HIAA, in the brain. We have recently demonstrated that PACAP-KO exhibits abnormalities in sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle. In the present study, behavioral responses to centrally acting drugs (amphetamine, haloperidol, risperidone, fluoxetine, and 8-OH-DPAT) were examined in PACAP-KO. Surprisingly, a psychostimulant amphetamine effectively normalized the deficit in PPI as well as hyperactivity and jumping behavior. These results implied phenotypic and pharmacological similarity between PACAP-KO and attention deficit hyperactivity disorder (ADHD). Although a potent dopamine D2-like receptor antagonist, haloperidol, ameliorated the hyperactivity and jumping behavior, it had no effect on the deficit in PPI. In contrast, a prototype of serotonin-dopamine antagonist (SDA), risperidone, effectively normalized the deficit in PPI as well as hyperactivity, and jumping behavior. A selective serotonin reuptake inhibitor (SSRI), fluoxetine, also suppressed the hyperactivity and jumping behavior. A 5-HT1A receptor agonist, 8-OH-DPAT, significantly lowered rectal temperature in wild-type mice, while it had only a small effect in PACAP-KO. These results suggest the involvement of dopaminergic and serotonergic dysfunction in phenotypic changes observed in PACAP-KO. (author abst.) |
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