The purpose of the present paper was to investigate the relationship of the serotonergic and dopaminergic systems to subscales of sensation seeking (SS). Two of the subscales, Disinhibition (DIS) and Experience Seeking (ES), were chosen for analysis based on their representation of the two major factors obtained in a factor analysis: DIS represents a factor of lack of impulse control and ES a factor of novelty seeking. In studies 1 and 2 responsivity to a serotonergic (5-HT) challenge by a 5-HT_1a receptor agonist (ipsapirone) was investigated by drug-induced prolactin (PRL) and cortisol responses, as well as by emotional states and behavioral measures. The dopaminergic (DA) response to a DA agonist (lisuride) and antagonist (fluphenazine) was analyzed in a condition of smoking deprivation (study 3) using PRL responses, emotional states, and behavioral measures of nicotine craving as dependent variables. In the studies of the serotonergic system, high ES subjects showed a blunted cortisol response in both studies and high DIS subjects demonstrated a blunted PRL response in study 2. A frequently observed side effect of serotonergic agonists, increase in emotional arousal, was not observable with ipsapirone in high ES and high DIS subjects as compared to low scorers. Behavioral aggression, which had been experimentally induced in study 2, was increased in high ES as well as in high DIS by the 5-HT_1a agonist which exerted antiaggressive effects in low scorers. These findings were found compatible with the idea of a generally low responsivity of the serotonergic system in high ES as well as in high DIS types of sensation seekers or 5-HT_1a subsensitivity in high DIS and subsensitivity of other postsynaptic 5-HT receptors in high ES. There was no association between SS subscales and DA-induced decrease of PRL, but high ES subjects seemed to tolerate nicotine deprivation better than low ES subjects indicating that they were less susceptible to deprivation of nicotine-induced DA. But craving for nicotine was increased in high ES subjects by the DA agonist lisuride as opposed to the antagonist, which was taken as evidence that DA stimulation may induce approach behavior in high ES. Although only two subscales had been selected for the investigation, this approach suggests both common and different relationships between SS subscales and neurotransmitter systems.

The magnitude of the cytosolic pool of acetylcholine in the cholinergic electromotor nerve terminals of Torpedo marmorata has been calculated to be 22 +/- 3% of the total by comparing the isotopic ratio of acetylcholine with that of choline when slices of electric organ were incubated with 10 microM deuterated choline. The calculation is based on a two-compartment model that assumes the presence, in unstimulated tissue, of a vesicular pool of acetylcholine that does not exchange, under resting conditions, with a second cytosolic pool; the latter, by contrast, is subject to 'futile recycling' and comes into isotopic equilibrium with the tissue choline pool.

The kinetics of recovery, by recycling electromotor synaptic vesicles, of the biophysical parameters of the reserve population has been studied in perfused blocks of electric organ of Torpedo marmorata prestimulated in vivo, followed by density gradient separation of the extracted vesicles in a zonal rotor using labile (acetylcholine and ATP) and stable (proteoglycan) vesicle markers. Stimulation in vivo at 0.15 Hz for 3.3 h depleted tissue acetylcholine much less than stimulation at 1 Hz for 1 h but nevertheless generated a much larger pool of recycled vesicles that recovered more slowly. At the lower rate of stimulation, recovery of the biophysical characteristics of the reserve population by the recycled vesicles, identified by their content of newly synthesized transmitter, was essentially complete by 8 h. The stable proteoglycan marker was immunochemically assayed and was bimodally distributed in the vesicle-containing portion of the density gradient even in experiments with unstimulated or recovered tissue. The second peak corresponded with that of newly synthesized transmitter and was thus identified as containing the recycled vesicles. Its normalized acetylcholine/proteoglycan ratio was lower than that of the first peak, which is consistent with earlier findings that recycled vesicles, before recovery, are only partially loaded with transmitter. However, as expected, the proportion of total vesicular proteoglycan and acetylcholine associated with the recycled vesicle fraction was very much lower in preparations derived from unstimulated or recovered tissue than in those from recently stimulated tissue.

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