Attenuation of induced-anxiety in rats by chlordiazepoxide: Role of raphe dorsalis benzodiazepine binding sites and serotoninergic neurons |
| |
Authors: | M.-H. Thiébot M. Hamon P. Soubrié |
| |
Affiliation: | 1. Département de Pharmacologie, Facultéde Médecine-C.H.U. Pitié-Salpêtrière, Paris, France;2. INSERM U.114, Collège de France, Paris, France |
| |
Abstract: | In chronically implanted awake rats, microinjections of chlordiazepoxide (5 × 10?7M) into the dorsal raphésignificantly attenuated the inhibition of lever-pressing for food elicited by a signal of punishment. This effect is abolished by prior application of 5,7-dihydroxytryptamine into the dorsal raphé(3 weeks after the infusion of the neurotoxin, dorsal raphétryptophan hydroxylase activity was reduced to 25% of control values). Furthermore, the disinhibitory effect of intra raphéchlordiazepoxide can be mimicked or potentiated by intra raphédorsalis application of serotonin (10?7 or 10?8 M, respectively). Further evidence for a crucial interaction between benzodiazepines and serotoninergic processes are provided by in vitro experiments showing that chlordiazepoxide or diazepam (10?5 M) are able to facilitate the K+ -evoked [3H]serotonin release from rat midbrain slices. Finally, a high density of [3H]flunitrazepam binding sites was found in the dorsal (and the median) raphénucleus, the Kd and Bmax values being not altered by prior infusion of 5,7-dihydroxytryptamine.These in vitro data suggest possible means by which intra raphé(and perhaps peripherally administered) benzodiazepines may affect the activity of serotoninergic neurons and thereby produce their effects on experimental anxiety. |
| |
Keywords: | 5-HT 5-hydroxytryptamine (serotonin) 5,7-DHT 5,7-dihydroxytryptamine GABA γ-aminobutyric acid CRF continuous reinforcement schedule |
本文献已被 ScienceDirect 等数据库收录! |
|