MODULATION OF 5HT(1A) RECEPTORS IN THE HIPPOCAMPUS AND THE RAPHE AREAOF RATS TREATED WITH CLONAZEPAM

1. Clonazepam is one of the most potent benzodiazepines known to decre ase the activity of the central serotonergic systems. The acute and su bchronic administration of clonazepam reduced serotonin (5HT) turnover rate in the hippocampus of the rat, as determined by the ratio of the monoamine and its metabolite. 5-hydroxyindoleacetic acid. 2. The modu lation of 5HT binding sites and 5HT1A receptors by the administration of clonazepam for various periods of time were studied in the hippocam pus and the raphe area by experiments with radioligands. 3. The densit y of [H-3]5HT recognition sites increased in the hippocampus of clonaz epam-treated rats in a dose- and time-dependent manner. This increase was impaired by the simultaneous administration of the 5HT agonist 5-m ethoxy-N,N-dimethyltryptamine. The affinity of this binding did not si gnificantly change. This observation might indicate an increase in som e of the 5HT receptors or an increase of the uptake site. 4. The bindi ng parameters for [H-3]DPAT, B(max) and K(d), decreased in the hippoca mpus but not in the raphe area of clonazepam-treated rats. It seems th at the presynaptic reduction in 5HT function, resulting in the decreas e of its availability at the synaptic space, modifies the correspondin g 5HT recognition sites. 5. These changes could be related to the anxy olitic activity or the withdrawal symptoms of benzodiazepines.