Evidence of roles of central alpha1-adrenoceptors and epinephrine in orexin A-induced hyperactivity in mice.
Previous studies have shown that central alpha1-adrenoceptor activity is necessary, acutely, for gross behavioral activity in response to novel surroundings and various psychostimulants. The present experiment tested whether it is also necessary for the hyperactivity produced by the peptide, orexin A, which is present in several central monoaminergic nuclei. Mice, pretreated intraventricularly with the alpha1-antagonist, terazosin, or the alpha2-antagonist, atipamezole, were given orexin A, intraventricularly (i.v.t.), and videotaped for gross movement and locomotion in the home cage between 30 and 60 min post-infusion. The alpha1-antagonist was found to produce a significant dose-dependent decrease of orexin A-induced activity, which was first seen at the 3 nmol dose and was near total at 30 nmol. The alpha2-antagonist, at 10 nmol, had no effect on the orexin A response. Pharmacological inhibition of the synthesis of epinephrine, a potential neurotransmitter at central motoric alpha1-adrenoceptors, with 2,3-dichloro-alpha-methylbenzylamine also significantly attenuated orexin A-induced hyperactivity. It is concluded that central alpha1-adrenoceptor activity, presumably caused by epinephrine release, is necessary for the gross behavioral activation produced by orexin A.
Stone
Eric A
EA
Department of Psychiatry, New York University School of Medicine, MHL-HN510, NYU Med Centre, 550 First Avenue, New York, NY 10016, USA. es35@nyu.edu
Lin
Yan
Y
Ahsan
Mohammad R
MR
Quartermain
David
D
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism*; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage*; D064446:Orexin Receptors; D000068797:Orexins; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011941:Receptors, Adrenergic; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C050701:atipamezole; C041226:Terazosin; D011224:Prazosin; D004837:Epinephrine