Effect of an atypical barbiturate, the 2-allophanyl-2-allyl-4-valerolactone (valofan), on exploratory behaviour and brain serotonin concentrations in mice.
This study investigates, both behaviourally and biochemically, the action of 2-allophanyl-2-allyl-4-valerolactone (Valofan) in the mouse, after acute or repeated administration. The exploratory behaviour was measured in different experimental conditions by a hole-board test modified in observation length: 10 min instead of original 5. The variations in 5-HT and 5-HIAA levels were measured in cortex and brainstem. Acute administration of Valofan (50 to 500 mg/kg os) did not change exploration during the first 5 min period, while at higher doses (200-500 mg/kg) it did produce a significant increase in basal exploratory behaviour, measured by prolonging hole-board test to 10 min. These data were confirmed by the habituation test to he thole-board whereby, after three days of exposure, low exploratory baseline of mice was constant. The elevation of the exploration was consistant with a significant net increase in 5-HT levels (greater than 5-HT; less than 5-HIAA) in brainstem, and with a relative enhance in amine levels (= 5-HT; less than 5-HIAA) in cortex for higher doses of the drug. Modifications of serotonin mechanisms positively affect behaviour in an unfamiliar environment. Surprisingly repeated treatment (for 8 days) with Valofan did not change exploration in respect of controls. The biochemical pattern of repeated treatments showed that higher doses of drug increased 5-HT without affecting 5-HIAA levels in brainstem and cortex. Repeatedly handheld mice showed control values significantly higher than those of acute treatment. This increase in activity corresponded to a biochemical pattern similar to that obtained after acute administration of 500 mg/kg Valofan, indicating that handling affected the basal 5-HT content. Thus Valofan could stimulate exploration in mice with a low baseline, while it did not change the activity of animals with a higher baseline. Further evidence for a possible involvement of 5-HT mechanisms in the action of Valofan was given by the fatigue test. Mice, submitted to hole-board after 24 h of forced walking, showed, with 500 mg/kg, a significant decrease in exploration: action of Valofan seemed to potentiate the effects exerted by stress on serotonin turnover.
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Traversa
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Puppini
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Jacquot
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Vertua
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013315:Stress, Psychological / Q000523:psychology; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014508:Urea; C000192:valofane