QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 10, 2006, 26(19):5091-5097; doi:10.1523/JNEUROSCI.4376-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Tanaka, K. Articles by Baba, A. Search for Related Content PubMed PubMed Citation Articles by Tanaka, K. Articles by Baba, A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB AMPHETAMINE

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits in Adcyap1-Deficient Mice

Kazuhiro Tanaka,^1 * Norihito Shintani,^1 * Hitoshi Hashimoto,¹ Naofumi Kawagishi,¹ Yukio Ago,^1,2 Toshio Matsuda,² Ryota Hashimoto,³ Hiroshi Kunugi,³ Akiko Yamamoto,¹ Chihiro Kawaguchi,¹ Takeshi Shimada,¹ and Akemichi Baba¹

¹Laboratories of Molecular Neuropharmacology and ²Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan, and ³Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan

Correspondence should be addressed to either of the following: Dr. Hitoshi Hashimoto, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan, Email: hasimoto{at}phs.osaka-u.ac.jp or Dr. Akemichi Baba, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan, baba{at}phs.osaka-u.ac.jp

Psychostimulants, including amphetamine, act as antihyperkinetic agents in humans with hyperkinetic disorder such as attention-deficit hyperactivity disorder and are known to be effective in enhancing attention-related processes; however, the underlying mechanisms have not been adequately addressed. Mice lacking the Adcyap1 gene encoding the neuropeptide pituitary adenylate cyclase-activating polypeptide (Adcyap1^–/–) display psychomotor abnormalities, including increased novelty-seeking behavior and hyperactivity. In this study, Adcyap1^–/– mice showed sensory-motor gating deficits, measured as deficits in prepulse inhibition (PPI), and showed normal PPI in response to amphetamine. Amphetamine also significantly decreased hyperlocomotion in Adcyap1^–/– mice, and this paradoxical antihyperkinetic effect depended on serotonin 1A (5-HT_1A) receptor signaling. c-Fos-positive neurons were increased in the prefrontal cortex in amphetamine-treated Adcyap1^–/– mice, suggesting increased inhibitory control by prefrontal neurons. Additionally, amphetamine produced an antihyperkinetic effect in wild-type mice that received the 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin. These results indicate that Adcyap1^–/– mice act as a model of hyperlocomotion and PPI deficits and suggest that 5-HT_1A-mediated pathways are important determinants of the psychostimulant-elicited, rate-dependent effects that are in a negative function of the baseline rate of activity.

Key words: neuropeptide; knock-out mice; psychostimulant; hyperactivity; prepulse inhibition; serotonin 5-HT_1A receptor

---

Received Oct. 13, 2005; revised March 24, 2006; accepted March 24, 2006.

Correspondence should be addressed to either of the following: Dr. Hitoshi Hashimoto, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan, Email: hasimoto{at}phs.osaka-u.ac.jp or Dr. Akemichi Baba, Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan, baba{at}phs.osaka-u.ac.jp

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2006 26: i. [Full Text]  

This article has been cited by other articles:

				D. Vaudry, A. Falluel-Morel, S. Bourgault, M. Basille, D. Burel, O. Wurtz, A. Fournier, B. K. C. Chow, H. Hashimoto, L. Galas, et al. Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery Pharmacol. Rev., September 1, 2009; 61(3): 283 - 357. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help