Role of alpha adrenoceptors in the nucleus accumbens in the control of accumbal noradrenaline efflux: a microdialysis study with freely moving rats.
Microdialysis technique was used to study the effects of the locally applied alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine-elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving rats. Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32% and phentolamine blocked this effect. Phentolamine elevated the basal noradrenaline efflux by 150% and phenylephrine counteracted this effect. The desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine and potentiated those of phentolamine. These results indicate that the accumbal noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are suggested to be presynaptically located on adrenergic nerve terminals in the NAc. Furthermore, this study suggests that the conformational state of alpha adrenoceptors varies across the available amount of noradrenaline. The clinical impact of these data is discussed.
Aono
Y
Y
Department of Pharmacology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Saigusa
T
T
Watanabe
S
S
Iwakami
T
T
Mizoguchi
N
N
Ikeda
H
H
Ishige
K
K
Tomiyama
K
K
Oi
Y
Y
Ueda
K
K
Rausch
W-D
WD
Waddington
J L
JL
Ito
Y
Y
Koshikawa
N
N
Cools
A R
AR
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine