The involvement of monoaminergic and GABAergic systems in locomotor inhibition produced by clobazam and diazepam in rats.
The effects of 1,5-benzodiazepine clobazam and diazepam were evaluated with regard to behavioral locomotor changes in rats. A concurrent focus of investigation was whether or not both benzodiazepines interact with central monoaminergic and GABAergic mechanisms. Diazepam was more active than clobazam in reducing locomotor activity. The stimulation of locomotor activity induced by L-dopa plus benserazide, and methamphetamine was significantly counteracted by diazepam but unaffected by clobazam. Hypomotility produced by alpha-methyl-p-tyrosine was markedly augmented with both drugs. Locomotor suppression elicited by 5-HTP, activating central serotoninergic transmission, was more potently reversed by clobazam than by diazepam. In addition, arousal behavior produced by p-CPA, inactivating central serotoninergic transmission, was completely abolished by both drugs. Furthermore, in combination with AOAA, known to inhibit motor activity, diazepam had a synergistic effect, and picrotoxin-produced suppression was significantly antagonized by diazepam. Both benzodiazepines thus may exert their behavioral depressant effects by reducing catecholaminergic and serotoninergic activity, and also by promoting GABA-mediated inhibition in the central nervous system. Clobazam is more effective than diazepam in reducing serotoninergic activity, but less effective in reducing catecholaminergic activity and increasing GABAergic activity.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000494:pharmacology*; D001679:Biogenic Amines / Q000502:physiology*; D000078306:Clobazam; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001679:Biogenic Amines; D001569:Benzodiazepines; D000078306:Clobazam; D005680:gamma-Aminobutyric Acid; D003975:Diazepam