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A new radioautographic technique for the visualization of central dopaminergic fibers is described. This technique is based upon in vitro uptake of triatiated norepinephrine or tritiated dopamine in the presence of monoamine oxidase inhibitor and specific uptake inhibitor in noradrenergic fibers. After a short step in glutaraldehyde, the use of osmium vapours as a fixative, instead of osmic acid immersion, allows a satisfactory retention of triatiated amines within dopaminergic fibers.

The present study investigated the mechanisms of the action of a tricyclic antidepressant, desmethylimipramine, upon paradoxical sleep in the rat in acute administration. Desmethylimipramine induces an increase in paradoxical sleep latency, as well as a decrease of its total duration; these two modifications are dose-dependent. Different mechanisms may be evoked: inhibition of catecholamine synthesis, inhibition of locus coeruleus by adrenergic collaterals, or an anticholinergic effect. The results show that inhibition of synthesis is not quantitatively sufficient to induce the observed effects. It appears more probable that this decrease in paradoxical sleep results from a collateral inhibition, with the possible participation of an anticholinergic effect. The contributions of these different factors are discussed.

Intraventricular injections of 5,7-DHT (.15 mg/g of brain weight) were performed in kittens aged 5 or 30 days. The neurotoxin induced a significant decrease of 5-HT and NA levels in the forebrain in both age groups, whereas a slight increase of each amine was observed respectively in the raphe and lateral brain stem of the younger group (Fig. 1). Pretreatment with desmethylimipramine (20 mg/kg I.P.) resulted in a protection of the noradrenergic system from the neurotoxin (Fig. 2). From the neurophysiological standpoint, 5,7-DHT induced a major paradoxical sleep (PS) insomnia in the one-month-old group, whereas no alteration of PS was observed in the younger group (Fig. 3). The DMI pre-treatment did not modify these results. The hypothesis of brain stem sprouting is discussed, and it is concluded that the serotoninergic system does not mediate the sleep regulation in the early post-natal period.

Incorporation of methionine into brain proteins has been measured by quantitative autoradiography after desmethylimipramine administration in rats. Acute treatment decreased protein synthesis in three regions: hippocampus, hypothalamus and habenula. After chronic treatment the decrease extended to four other regions: substantia nigra, raphe dorsalis, trigeminal nerve and hypophysis. An opposite effect was observed in the retrosplenial cortex.