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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Nishino, S. Articles by Mignot, E. Search for Related Content PubMed PubMed Citation Articles by Nishino, S. Articles by Mignot, E.

 Previous Article  |  Next Article 

Journal of Neuroscience, Vol 11, 2666-2671, Copyright © 1991 by Society for Neuroscience

ARTICLE

Dopamine D2 mechanisms in canine narcolepsy

S Nishino, J Arrigoni, D Valtier, JD Miller, C Guilleminault, WC Dement and E Mignot
Stanford Sleep Disorders Research Center, Palo Alto, California 94304.

Narcolepsy is a sleep disorder characterized by abnormal manifestations of rapid-eye-movement (REM) sleep and excessive daytime sleepiness. Using a canine model of the disease, we found that central D2 antagonists suppressed cataplexy, a form of REM-sleep atonia occurring in narcolepsy, whereas this symptom was aggravated by D2 agonists. The effect on cataplexy was stereospecific for the S(-) enantiomer of sulpiride (a D2 antagonist) and the R(+) enantiomer of 3-PPP (a D2 agonist). There was also a significant correlation between the in vivo pharmacological potency and in vitro drug affinity for D2 receptors (but not for D1 and alpha 2 receptors) among the seven central D2 antagonists tested. Selective D1 compounds were also tested; however, the results were inconsistent because both antagonists and agonists generally suppressed cataplexy. Our current results demonstrate that central D2-type receptors are critically involved in the control of cataplexy and REM sleep. Furthermore, the finding that small doses of D2 antagonists suppressed cataplexy and induced behavioral excitation, while small doses of D2 agonists aggravated cataplexy and induced sedation, suggests that this effect is mediated presynaptically. However, considering the fact that selective dopamine reuptake inhibitors did not modify cataplexy and that our previous pharmacological results demonstrated a preferential involvement of the noradrenergic system in the control of cataplexy, we believe that the effect of D2 compounds on cataplexy is mediated secondarily via the noradrenergic systems.

This article has been cited by other articles:

				K. Takakusaki, K. Takahashi, K. Saitoh, H. Harada, T. Okumura, Y. Kayama, and Y. Koyama Orexinergic projections to the cat midbrain mediate alternation of emotional behavioural states from locomotion to cataplexy J. Physiol., November 1, 2005; 568(3): 1003 - 1020. [Abstract] [Full Text] [PDF]

				C. W. Olanow, A. H. V. Schapira, T. Roth, W. J. Weiner, M. M. Hoehn, A. Lledo, J. Nash, F. M. Arellano, M. Corrigan, G. Arnold, et al. Falling asleep at the wheel: Motor vehicle mishaps in people taking pramipexole and ropinirole Neurology, January 11, 2000; 54(1): 274 - 274. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help