Effects of stress on the functional properties of pre- and postsynaptic 5-HT1B receptors in the rat brain.
Numerous studies have clearly shown that the turnover and release of serotonin (5-hydroxytryptamine, 5-HT) are increased under acute stressful conditions. Inasmuch as this latter process is under the control of a feedback mechanism involving the stimulation of presynaptic 5-HT1B autoreceptors, we have investigated the possible effects of acute restraint (40 min) on the functional properties of 5-HT1B receptors. The efficacy of the selective 5-HT1B receptor agonist 3-[1,2,5,6-tetrahydropyrid-4-yl]pyrrolo-[3,2-b]pyrid-5-one (CP-93,129) in inhibiting in vitro the K+-evoked release of [3H]5-HT, was significantly reduced in stressed rats as compared to naive animals. Similarly, the responsiveness of 5-HT1B receptors inhibiting the release of [3H]acetylcholine (presynaptic 5-HT1B heteroreceptors), was reduced by restraint. These effects were observed in the hippocampus, but using the inhibitory effect of CP-93,129 on forskolin-stimulated adenylyl cyclase activity as an index of 5-HT1B receptor function, it could be shown that the 5-HT1B receptors located in the substantia nigra are also desensitized by stress. The number as well as the apparent affinity constant of 5-HT1B binding sites labelled by [125I]iodocyanopindolol, as measured by quantitative autoradiography and membrane binding, were similar in naive and restraint-stressed rats suggesting that the stress-induced desensitization of 5-HT1B receptors is not due to a reduced number of 5-HT1B binding sites. As stress is thought to be a causal factor for the etiology of anxiety and depression, these results support the potential involvement of 5-HT1B receptor dysfunction in the development of these neurological disorders.
Bolanos-Jimenez
F
F
Unite de Pharmacologie Neuro-Immuno-Endocrinienne de l'Institut Pasteur, Paris, France.
Manhaes de Castro
R M
RM
Seguin
L
L
Cloez-Tayarani
I
I
Monneret
V
V
Drieu
K
K
Fillion
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017660:Autoreceptors / Q000502:physiology; D001921:Brain / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D020120:Iodocyanopindolol; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology*
D017660:Autoreceptors; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012701:Serotonin; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D003345:Corticosterone