Attenuation of induced-anxiety in rats by chlordiazepoxide: Role of raphe dorsalis benzodiazepine binding sites and serotoninergic neurons

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 B_max 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.