Region-selective reduction of brain serotonin turnover rate and serotonin agonist-induced behavior in mice treated with clonazepam.
Evidence supports a complex interaction between benzodiazepines and the central serotonergic system. This study attempts to correlate biochemical changes in the serotonin (5HT) system induced by clonazepam (CLON) with the behavioural response to a 5HT agonist. The acute administration of CLON to mice produced a time-dependent decrease in 5HT turnover rate in the raphe area (dorsal and medial raphe nuclei) and modified the serotonergic syndrome induced by 5-methoxy-N,N,-dimethyltryptamine (DMT). One hour after CLON administration, a dose-dependent increase in 5HT concentration was found in the raphe area, while 5-hydroxyindoleacetic acid (5HIAA) levels remained stable, leading to an increase in 5HT/5HIAA ratio, indicative of reduced 5HT turnover rate. No significant changes were detected in the frontal cortex of CLON-treated mice. After 4 days of CLON treatment, the 5HT turnover rate was still decreased in the raphe area and unchanged in the frontal cortex. Acute CLON administration produced dose-dependent alterations in locomotor activity, not observed after subchronic administration. Lateral head weaving, a motor manifestation of the serotonergic syndrome produced by DMT, was less intense in CLON-treated animals. The modifications in the 5HT system induced by CLON are region selective, suggesting differences in the receptors implicated in the interaction. Altered synaptic availability of 5HT as a result of CLON administration may be responsible for the differential response to DMT in control and CLON-treated mice.
Lima
L
L
Instituto Venezolano de Investigaciones Cientificas, Laboratorio de Neuroquímica, Caracas.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002998:Clonazepam / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology
D008732:Methoxydimethyltryptamines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002998:Clonazepam