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In order to investigate the link between aggression and 5-HT, we looked at effects of changes in plasma tryptophan on healthy male subjects. Twenty-four with high trait aggression (H) and 24 with low (L) drank an amino acid mixture with (T+) or without (T-) tryptophan. These caused plasma tryptophan enhancement and depletion, respectively, at 4.5 h. Group H subjects given T- became more angry, aggressive, annoyed, hostile and quarrelsome on subjective measures, whereas those given T+ responded in the opposite way. On a behavioural measure of aggression, group H subjects responded more aggressively after T- than T+. In contrast, there was no consistent effect on subjective or behavioural aggression in group L subjects. Feelings of well-being in group H were decreased by T- and increased by T+. In group L, T+ reduced feelings of well-being, possibly due to the sedative effect of tryptophan in this group, which correlated positively with plasma tryptophan concentration. Changes in plasma tryptophan are probably followed by changes in central 5-HT turnover. We conclude that, in those with pre-existing aggressive traits, acute falls in central 5-HT can cause increased subjective and objective aggression, while rises can have the opposite effect. The absence of changes in a low aggressive group suggests that the primary effect may be on impulsivity, possibly mediated by 5-HT1a receptors, expressing underlying aggressive traits. The findings on mood changes provide support for earlier reports of a lowering of mood with tryptophan depletion.

Within triads of male Wistar rats, some animals almost completely abstain from competition for palatable sucrose pellets (so-called poor-performing rats), whereas other rats consistently win the competition (so-called high-performing rats). Subchronic (5 mg/kg; 5 consecutive days), but not acute (0.1-20 mg/kg), treatment with chlordiazepoxide temporarily helped poor-performing rats to behave more competitively. This finding, considered together with parallel studies (using high-performing rats), suggested that chlordiazepoxide's beneficial effect was only demonstrable when the poor-performing rats had become tolerant to the drug's initial sedative effect.

In a double-blind, balanced crossover study, eight healthy male volunteers ingested either DL-308 (10 mg), DL-308 (20 mg), oxazepam (30 mg) or placebo. Subjective estimates of coordination and anxiety, objective performance measurements and cardiovascular measurements were taken at 1, 3, 5 and 8 h after ingestion. DL-308 (20 mg) exerted a strong sedative effect as judged by self-reported coordination scores and performance on logical reasoning and reaction time tests. The effect was evident almost immediately and, on the coordination and reasoning tests, lasted up to 8 h following ingestion. Attention is drawn to the need to extend performance testing in order to maximise test sensitivity. No drug had any consistent or strong influence on cardiovascular measures.

In order to clarify the influences of situational factors on the effects of psychotropic drugs, the sedative effects of tetrabenazine after injection at various times of the day were studied. When 50 mg/kg body weight of tetrabenazine was injected into rats at eight different times of the day (07∶30–19∶30 dark, 19∶30–07∶30 light), a circadian rhythm of sedative effect was observed with a peak sedative time of 1490 min at 10∶30 and a nadir of 736 min at 07∶30. With 10 mg/kg body weight of tetrabenazine a similar circadian rhythm of sedative effect was observed. This rhythm did not appear to be due to differences of metabolism of tetrabenazine in the tissues, but rather to be closely related to daily fluctuation of serotonin synthesis and release in the brain.